The spectrum of ASIA: ‘Autoimmune (Auto-inflammatory) Syndrome induced by Adjuvants’

1.        N Agmon-Levin1

2.        GRV Hughes2

3.        Y Shoenfeld1,3

1.        1The Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel
2.        2Head, Lupus Research Unit, The Rayne Institute, St. Thomas' Hospital, London, UK
3.        3Sackler Faculty of Medicine, Incumbent of the Laura Schwarz-KipChair for Research of Autoimmune Diseases, Tel-Aviv University, Israel

1.        Yehuda Shoenfeld, MD, FRCP, Zabludowicz Center for Autoimmune Diseases, Chaim Sheba Medical Center, Tel-Hashomer 52621, Israel. Email:

Physicians are often puzzled by enigmatic medical conditions or the abrupt appearance of an immune-mediated disease. Such a story was recently presented to us by a young Sheikh. A Saudi Sheikh, who suffered at the age of 27 from joints pains, rash and serological evidence of anti-Ro antibodies, was diagnosed with probable systemic lupus erythematosus (SLE) at that time. He was treated with Plaquenil for a year, but as no signs of SLE were apparent, treatment was stopped and he remained disease free for the next 12 years. At the age of 39 years, 2 weeks after immunization with the flu vaccine, his disease reemerged. This time he presented with severe arthritis and pericarditis, which required treatment with high doses of steroids.

This patient’s story illustrates the acceleration of an autoimmune or immune-mediated condition following exposure to external stimuli. During the past year a new syndrome was introduced and termed ASIA, ‘Autoimmune (Auto-inflammatory) Syndrome induced by Adjuvants’.1 This syndrome assembles a spectrum of immune-mediated diseases triggered by an adjuvant stimulus.2 4 The use of medical adjuvants has become common practice and substances such as aluminum adjuvant are added to most human and animal vaccines, while the adjuvant silicone is extensively used for breast implants and cosmetic procedures. Furthermore, ‘hidden adjuvants’ such as infectious material or house molds have also been associated with different immune mediated conditions.1,5 The adjuvant effect has been recognized for years, and is broadly utilized to enhance desired antigen-specific immune responses.6 This effect is accomplished via mechanisms that impinge on both the innate and adaptive immune systems.6 9 Formerly, adjuvants were thought to pose little or no independent threat. Alas, studies of animal models and humans demonstrated the ability of some of them to inflict autoimmunity and immune-mediated diseases by themselves.2,10,11 Intriguingly, although exposure is common, adjuvant disease is relatively rare. It has been suggested that for a clinically overt adjuvant disease additional risk factors are required such as genetic susceptibilities or the co-exposure to other environmental factors.1

This special issue of Lupus is dedicated to ASIA and contains diverse articles from different geographical areas which provide a broad view of the clinical manifestations as well as the mechanisms related to the adjuvant effect.

The link between silicone, a synthetic polymer, and immune-mediated diseases has been accepted by the medical community and is one of the cornerstones of ASIA.1,4 Nevertheless, the association between ‘siliconosis’ and systemic sclerosis remains controversial4 and is reviewed herein by Lidar et al.12 This review describes the mechanisms by which silicones mediate autoimmunity in general as well as the evidence for a casual association between this adjuvant and specific autoimmune diseases, such as systemic sclerosis. Following the same path Kivity et al.13 present the case of a patient from the Middle East diagnosed with an overlap between morphea and eosinophilic fasciitis in association with breast implants. This silicone-related skin disease is within the spectrum of systemic sclerosis. From the other side of the globe Jara et al.14 and Vera-Lastra et al.15 report a patient with Still’s disease after silicone implantation as well as a cohort of patients with severe local and systemic diseases following the illegal use of oil adjuvants for cosmetic purposes. The latter comprise of 50 patients, of which 41 were injected with mineral oil and 9 with other substances (e.g. iodide gadital, guyacol). Thirty of them presented with non-specific autoimmune disease and 20 fulfilled the criteria for a defined autoimmune-rheumatic disease.

Another cornerstone of ASIA is the complex interaction between autoimmunity and adjuvanted vaccines. On the one hand vaccines are beneficial for the vast majority of subjects including those who suffer from autoimmune-rheumatic diseases as delineated in this issue by van Assen and Bijl.16 On the other hand in a small minority of individuals vaccine can trigger the appearance of autoantibodies as documented by Vista et al.17 and Perdan-Pirkmajer et al.18 Moreover, a link between immunization and defined autoimmune diseases has been reported elsewhere and herein.2 A plausible association between the flu vaccine and polymyalgia rheumatica is reported here by Soriano et al.19 from Italy, and Soldevilla et al.20 describe three patients diagnosed with SLE following immunization with the human papilloma vaccine from the Philippines. In addition, in a retrospective analysis Zafrir et al.21 details common denominators among 93 American patients diagnosed with immune-mediated conditions following inoculation with hepatitis B vaccine. In this cohort although different autoimmune diseases were diagnosed, many manifestation were common to all patients and 86% of them fulfilled the criteria for ASIA. Of note, these cohorts signify only one side of the ASIA spectrum as they cope with distinct immune-mediated diseases while ASIA also comprises enigmatic and non-defined medical conditions. Two such conditions, the macrophagic myofasciitic syndrome and the Gulf War syndrome, are thus reviewed in this special issue by Gherardi and Authier22 and Israeli.23

Although amassed clinical data has been presented in support of an association between adjuvants and immune-mediated diseases the proof of causality remains a challenge. Hence, in this issue two experimental models are portrayed, both of which prove the concept of autoimmunity induced by adjuvants. The induction of anti-phospholipid syndrome (APS) in two non-autoimmune prone mice strains, BALB/c and C57BL/6 via hyper-immunization with tetanus vaccine is reported by Dimitrijević et al.24 APS, the Hughes syndrome, is characterized by obstetric morbidity and/or thrombosis and the presence of anti-phospholipid antibodies. In this model immunization with tetanus toxoid and different adjuvants (glycerol or aluminium hydroxide) or different adjuvant pretreatments (glycerol or CFA) induced pathogenic anti-phospholipid autoantibodies as well as fetal resorptions and reduced fecundity. In another model, NZBWF1 mice that are genetically prone to develop SLE were immunized with complete Freunds’ adjuvant. Acceleration of SLE-like disease was observed as reported by Bassi et al.25 In addition, the state of the art regarding oil adjuvants and autoimmunity is presented in this issue by Whitehouse,26 while the various mechanisms of aluminium toxicity both in pediatric populations as in patients diagnosed with Crohn’s disease are illustrated by Tomljenovic and Shaw27 and Lerner.28

Taken together, this global view of ASIA probably represents only the tip of the iceberg. Encouraging physicians and patients to report adjuvant-related conditions will enable a better estimation of the true prevalence as well as the width of ASIA spectrum.1,29 It seems that the role of adjuvants in the pathogenesis of immune-mediated diseases can no longer be ignored, and the medical community must look towards producing safer adjuvants. Studies that will address individual risk factors as well as different adjuvant-related ones are therefore urgently needed.

Meanwhile, reflecting on our patient, the young Sheikh, one might suggest that he was genetically prone to develop SLE and the exposure to the adjuvanted flu vaccine, simply triggered his malfunctioning immune system. Therefore, although immunization with the flu vaccine is considered safe for most SLE patients, for this particular patient, re-immunization should be considered with caution.


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This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

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Conflict of interest statement

The authors declare no conflicts of interest expect for Y Shoenfeld, who has appeared in court for cases of vaccine injuries.

*          © The Author(s), 2012. Reprints and permissions:

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Infect Dis Clin North Am. 2011 Dec;25(4):851-63. Epub 2011 Sep 9.

The Common Immunogenic Etiology of Chronic Fatigue Syndrome: From Infections to Vaccines via Adjuvants to the ASIA Syndrome.


Department of Medicine B, Sheba Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Tel-Hashomer 52621, Israel; Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Tel-Hashomer 52621, Israel.


Chronic fatigue syndrome (CFS) is characterized by unexplained fatigue that lasts for at least 6 months with a constellation of other symptoms. Most cases start suddenly, and are usually accompanied by a flu-like illness. It is a symptom-based diagnosis of exclusion, the pathogenesis of which is unknown. Studies have examined and hypothesized about the possible biomedical and epidemiologic characteristics of the disease, including genetic predisposition, infections, endocrine abnormalities, and immune dysfunction and psychological and psychosocial factors. Recently, the AISA (autoimmune/inflammatory syndrome induced by adjuvants) syndrome was recognized, indicating the possible contribution of adjuvants and vaccines to the development of autoimmunity.

Copyright © 2011 Elsevier Inc. All rights reserved.

[PubMed - in process]


The Hayward Foundation Study on Vaccines

For 15 years, some Great Dane breeders have postulated the adverse effects of the aggressive use of vaccines on the immature (puppy) immune system.  This concern led these breeders to a more conservative approach to vaccinations, the monitoring of antibody titers before boosters were given, or in some cases safe alternatives to conventional practice were invoked. 

Over the last two years a cutting edge scientific research study has been conducted at Purdue University, under the direction of Larry Glickman, VDM,PhD and his associate Dr. Harm HogenEsch (Curricula Vitae and the impressive credentials of these scientists are included for your review). The study proposal is to investigate the autoimmune responses to vaccines in dogs. This study, at Purdue, was conceptualized by Great Dane people, and subsequently funded (± $175,000.00) by a Great Dane friendly organization called the John & Winifred Hayward Foundation. Originally, it was considered ideal to conduct the study with a colony of Great Danes.  However, the feasibility and practicality of maintaining and housing a controlled group of Great Danes was economically out of reach.  Therefore, the study identified the Beagle as the canine of choice, but recognized the applications of any results to the canine population as a whole, including Great Danes.

The study has produced some dramatic results, with concrete and clear evidence that there are adverse events elicited as a result of the use of vaccines following manufacturer's recommendations. (Review the following article for a more complete picture of study results.)

 In Dr. LaRosa's (Trustee of the Hayward Foundation) article (following), he states that a number of autoantibodies to several critical proteins and DNA were identified in the vaccinated group. Identifying these autoimmune antibodies, and monitoring their titers may lead, in addition to the thyroiditis conditions, a better understanding of the role of vaccines in soliciting adverse events that contribute to problematic conditions observed in the Great Dane, such as Cardiomyopathy, and Various Bone related disorders.

The positive outcomes of the study at Purdue will hopefully be the identification of a number of genetic markers that will facilitate a brighter and healthier future for our breed, as well as recommendations for safer vaccines and their uses.

The Hayward Foundation is limited by its charter to investigate Human Genetic Disorders, therefore its ability to significantly fund this study further falls outside of the realm of its charter.  However, the Trustees of the Hayward Foundation have committed an additional $25,000.00 to help in the maintenance of this colony until further funding is identified.

Glickman has stated that the colony will be lost unless further and immediate funding is identified to maintain the colony .  Dr. Glickman is applying to the AKC Foundation and the NIH (National Institute of Health) for funding. Two years of research will not be lost but the future of this work which relies on maintaining the colony for some time to come will be lost.


A Possible Etiology of Autoimmune Diseases

By : William R. La Rosa, M.D. (Trustee)

The Hayward Foundation is dedicated to research and eradication of human genetic diseases.  There is much anecdotal hearsay about the safety of vaccines in dogs as well as in humans.  The Vaccine Safety Committee recently emphasized the need for more definitive research on possible adverse effects during the development of new vaccines and vaccine combinations. (National Academy Press, Washington D.C. 1994).

When a dog vaccine safety issue was brought to our attention by Laura Kiaulenas, a prominent Harlequin Great Dane breeder, and after reading articles by Jean Dodds DVM, we decided to fund a study to prove or disprove the supposition of multiple diseases, acute and chronic, caused by vaccination.  If indeed, many breeders are correct, then is the dog a canary sentinel, and are human similarly being affected, and if so can we identify the dog or human who is genetically susceptible to these reactions ?

We were fortunate that prominent and respected researchers, Drs. Larry T. Glickman, Harm HogenEsch, Juan I. Azona-Olivera, J. Catherine Scott-Montcrieff, and Paul W. Snyder of Purdue University, School of Veterinary Medicine, agreed to undertake the study.  The results are enlightening and they are enthusiastically working on the second phase, a study of longer duration.

They presented a paper to the International Veterinary Vaccines and Diagnostics Conference, July 27 - 31, 1997, in Madison, Wisconsin, hosted by the University of Wisconsin.  These proceedings have been published in  Advances in Veterinary Science and Comparative Medicine . Another manuscript:  Vaccine Induced Serum Autoantibodies in Young Beagles , has been submitted to a human immunology journal  Clinical Immunology and Immmunopathology.

Their study was based on the increasing concern among veterinarians and breeders that current vaccination protocols adversely affect the health of dogs.  This concern has largely been based on anecdotal and circumstantial evidence.  They studied the effects of routinely used vaccination protocol on the immune and endocrine systems of Beagles.

One control group was not vaccinated and the other group was vaccinated with a commercial multivalent vaccine at 8, 10, 12, 16, and 20 weeks of age and with a rabies vaccine at 16 weeks of age. A definition of autoimmune disease is now necessary.  In dogs as well as humans, the body sometimes forms antibodies against itself (self antigens) which can lead to diseases of the pancreas (diabetes), thyroid (Hashimoto's Disease), collagen and fibronectin (Scleroderma, Lupus),cardiolipin (Cardiomyopathy), etc.  The body literally attacks itself to cause the autoimmune disease. 

The vaccinated group developed significant levels of autoantibodies against: fibronectin, laminin, DNA, albumin, Cytochrome C, transferrin, cardiolipin, collagen. The responses varied among individual animals, probably reflecting genetic differences.  The clinical significance of those autoantibodies remains to be determined, but speculation must be that something in the vaccines is one of the etiologies (in the genetically susceptible dog) of such diseases as Cardiomyopathy, Lupus Erythematosus, Glomerulonephritis, etc.  I apologise for using these technical terms but this is a complex study and adds validity to the report. Autoimmune diseases are quite common in dogs as well as in humans, but much easier to study in dogs, especially since various breeds have genetic susceptibility or predisposition.  The high prevalence of autoimmune disease in specific breeds makes it easier to search for the genetic markers.  Humans are much more diverse and therefore more difficult to study.

 We hope that many Breed Associations and the AKC Foundation will join us in expanding these studies with the needed research funds.  Longer term studies are needed to determine the clinical importance of vaccine-induced autoantibodies and to identify markers of genetic susceptibility.  These are truly remarkable results.  The next step is to study the development of safer vaccines, or possibly modify the recommended dosages, and the timing of vaccinations.  Many vaccines, including a vaccine for use in humans, contain fibronectin.  This appears to be a common contaminant.  Other antigens will be studied. 

A general theme of the Conference was that vaccine immunity lasts longer than the manufacturer claims; rabies is probably effective for at least 3 years and we are probably over-vaccinating our dogs.  Even the vaccine industry tells you that there is never 100% protection.  Therefore disease is seen even in vaccinated groups.  In Europe, vaccines are prohibited once the disease is eliminated because the fear of reversion to virulence of the modified live virus. 

Autoimmune diseases in dogs are clinically similar to those in humans. We hope that Veterinary and Medical Schools will continue and expand these preliminary research studies.  Our companion dogs are crashing all around us and maybe we are now finding one of the sources of the problems.  It has been so easy to point fingers at breeders but they may not be entirely at fault.  Let us continue this important research to help our future generations of dogs and possibly children.  Yes, indiscriminate breeding can genetically predispose the dog but is the trigger mechanism indiscriminate vaccinations?

 My personal interpretation of the above information in brief is: (from Dr. La Rosa MD) 

1.  These studies appear to support the conclusions of some breeders that multiple vaccinations may be harmful to dogs.  Be cautious and keep current in the scientific literature.

2.  Current vaccines induce autoantibodies. Contaminants may be part of the problem.

3.  We need to research and explain the mechanism.  Does it alter the DNA causing genetic abnormality or is the susceptible gene already in place? Can we find the genetic marker to avoid the adverse reaction of vaccination ?

4.  The dog is a good model for study because different breeds already have susceptibility to specific diseases and genetic markers will be easier to find than in other diverse animals (and humans).

5.  What is the solution or cure, and especially how is this applicable to humans.

6.  Most current vaccines are effective in preventing disease, but they may be administered more frequently than is actually required.

This study certainly points out the preliminary conclusions that have also been done with the Canine Health Concern in the UK .

Breed clubs interested in contributing to further research on vaccines may contact:

William R. La Rosa M.D. (Trustee, John & Winifred Hayward Foundation)

(352) 799-5202



Effects Of Vaccination On The Endocrine And Immune Systems of Dogs

Phase II

Purdue University, November 1, 1999

Drs. Harm HogenEsch and Larry T. Glickman

Concern has been growing among owners, breeders, and veterinarians that current vaccines cause immune-mediated diseases in dogs.  Vaccination is highly effective in preventing infectious disease, but the safety of many vaccines and the frequency of their administration are being questioned.  The Vaccine Research Group at the Purdue University School

of Veterinary Medicine has been conducting several studies to address these issues. In one such study, we are trying to determine if current vaccines cause changes in the immune system of the dog that will eventually result in life-threatening immune mediated diseases. 

 The Beagles being used in this study were bred by us and then vaccinated following a typical schedule used for pet dogs.  These Beagles have been closely followed for three years with blood and other tests performed at regular intervals.

 To date, routing vaccination of these Beagles has not caused any overt signs of clinical disease.  However, the blood of all the vaccinated dogs contains significantly elevated concentrations of antibodies directed against proteins that are present in commercial vaccines as contaminants of the production process.  None of the unvaccinated control dogs has had a similar increase in these antibodies.  These proteins are typically of bovine origin since fetal calf serum is used to grow the viruses for vaccine production.  The close similarity in structure of the bovine proteins to dog proteins results in a situation whereby the antibodies produced by the vaccinated dogs may cross-react with dog tissue proteins in a process similar to autoimmunity.

 Experiments in other animal species suggest that these autoantibodies might eventually cause diseases in the vaccinated animals, but these Beagle dogs will need to be followed longer to determine if this is the case.  In addition, the pattern of individual responses of the immune

system to vaccination in this study suggests a possible genetic predisposition to autoimmunity.

 The study described above is unique in that it attempts to determine if vaccinations that dogs routinely receive throughout their life have a cumulative adverse effect.  The only way this is possible is under experimental conditions where one group of dogs remains unvaccinated.

The vaccine studies we are conducting both in Beagles and in pet dogs under natural conditions are designed to answer the question: "Does vaccination play a role in autoimmunity, how safe are currently used vaccines, and how often should these vaccines be administered?"

FURTHER UPDATE: In March, 2000 I personally contacted Dr. Glickman regarding this study and in the course of events that followed; Dr. Glickman has agreed to extend the study to our breed, the Great Dane. In the initial conversations, Dr. Glickman postulated that to continue the study further would cost in the neighborhood of one to two million dollars. When I told him that we have a number of Great Danes that are totally unvaccinated and could act as 'controls'. he came back very excited and proposed the further study with Great Danes. With the help of my good friend Magda Aquila and the internet we managed to get a total of 80 Danes to participate in the study.

The Study will be divided into 3 groups: Unvaccinated..; Vaccinated without annual boosters and Vaccinated with annual boosters.

Stay tuned as we will keep you updated to the progress of this very important study.

A 'Jello Theory of Autism', Anyone?

      By 1930 vaccines were being cultured in either agarose gel or egg culture and vaccines are still grown in these conditions. By 1942 Kanner reported on the existence of autism. These cultures contain naked DNA as heat shock protein 72 kDa. Heat shock proteins cross all living species from plant, viral pathogens including measles, cytomegalovirus and candida and single celled animals to humans. The protein coating on immune cells that tell a living thing when to respond to injury, pathogen, environment, stress.  In autism studies measles containing the 72 kDa heat shock protein are found in every cell which contains the measles virus. Gut dysbiosis is common and candida overgrowth is often identified.

      Science recommends that infants and toddlers with neurodevelopmental delay, autoimmune weakness and food allergy to egg and now gelatin not receive vaccination. Infants are vaccinated in the nursery at birth, is science following its own guidelines. Do those who provide policy and procedure for vaccination schedule have any method of determining who is at risk for neurodevelopmental delay and autoimmune weakness? Yes, in fact they do. Molecular biology research has provided substantial information that at least ten percent and up to twenty percent of the human population have autoimmune phenomena which can be traced to vaccination. In some populations the autoimmune phenomena or evolution of the immune system has resulted in celiac disease, in other populations spontaneous abortion, in the general population diabetes, lupus and arthritis. A simple question which should be used as a measure to recommend a delay in the vaccine schedule at the very least or a recommendation for testing to determine immune response to egg and gelatin before vaccinating  would be - is there a family history of autoimmune disease. Autism research continues to include that a significant percent of those families who have a child or children with autism have also autoimmune disease.

      More common than autoimmune disease is genetic diversity, children with autism born to families where ancestry is mixed. When the family history is of mixed ancestry and there is also a history of autoimmune phenomena then the presentation of autism is generally more severe.  Plant foods and particularly those containing lutein, a pigment derived from chlorophyll from which the plant color can become red, green, yellow or orange during ripening have the 72 kDa heat shock protein coating.

      Humans had never gotten a virus from plant foods but the development of vaccines resulted in the immune system being presented with viral pathogen and heat shock protein simultaneously. A wolf in sheeps clothing, a Trojan horse? The immune system evolves and information is stored in our genes and passed to the next generation. During fetal development the developing infants immune system uses the genetic information and alters our development. The immune system must first identify a pathogen and  a substance associated with heat shock protein 72 kDa that commonly crosses the placental barrier  is lutein. Lutein and carotenoids easily pass into breast milk and both Kanner and Asperger reported on the difficulty in feeding for infants later identified with these conditions.

      Unfortunately science left this characteristic of autism out of the main body of literature for diagnosing a child with autism. Feeding problems, fear of food and unusual relationship to foods remain as a primary characteristic of autism. Infants and children with autism desperately trying to avoid the foods which their bodies experience as pathogen. Foods which contain substances which are like poison to their bodies. Foods which cause their immune system to produce elevated levels of small immune cells which in turn allow their bodies to produce increasing numbers of macrophage cells, like a pac man cell that removes toxins and produces antibodies. As the number and types of food increase in the childs diet, which excite the immune system, the potential for a vaccine reaction also increases. What the child is being fed at the time of vaccination can contribute to vaccine reaction.

      Science currently has been looking at using the heat shock protein as vaccine chaperones (carriers). This research has led to WARNING as the discovery of damage and autoimmune phenomena in the offspring of animals vaccinated using this method has become known. But, science has been unwittingly using this method for nearly a century.   Autism does have a cause and the primary treatment option is dietary intervention.
      - Sandra Desorgher MA-TFM, MA-FSN
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Borchers AT, Keen CL, Shoenfeld Y, Silva J Jr, Gershwin ME.

Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, Davis, CA, USA.

Vaccinations are invaluable in protection from a wide variety of diseases that can cause substantial morbidity and mortality. Although a rare complication of vaccination, autoimmune disorders represent one of these morbidities. Recently, widespread public concern has arisen from case reports suggesting that--similar to what has been observed after natural viral infections--there might be an association between specific immunizations and autoimmune diseases. Herein we address the biological plausibility of such a connection, focusing particularly on the examples of hepatitis B, rubella, and measles-mumps-rubella (MMR) vaccinations, and the autoimmune diseases they are potentially associated with. Our review of the available data suggests that, for the general population, the risk: benefit ratio is overwhelmingly in favor of vaccinations. However, the possibility cannot be ruled out that, in genetically susceptible individuals, vaccination can result in the unmasking of an autoimmune disease triggered by the immunization. We also critically examine the existing data suggesting a link between immunization against MMR and autism, and briefly discuss the controversial evidence pointing to a possible relationship between mercury exposure from vaccines and autistic disorders. There is a continued urgent need for rigorously designed and executed studies addressing these potential associations, although the use of vaccinations remains a critical public health tool for protection against infectious disease.

CBC News: Canadians aim for long-term remission from MS

Canadians aim for long-term remission from MS
Last Updated Mon, 31 Mar 2003 18:49:38

OTTAWA - Canadian doctors are reporting encouraging early results from an experiment designed to replace the immune system of multiple sclerosis patients. Multiple sclerosis starts with a faulty immune system that attacks the protecting coating on nerves. There is no cure for the disease. The few drugs that are available are not working for John McCleary and his MS is advancing quickly. He is gambling on a risky experiment that might stop MS in its tracks. "The way medicine is progressing, something else can come down the road that might reverse the symptoms," said McCleary. Ottawa neurologist Dr. Mark Freedman is behind the radical new approach. "Well, we know it's a problem with the (immune) system, so we now have the tools to replace the entire system," said Freedman.

Doctors harvested stem cells from McCleary's blood and purified the cells to remove all traces of MS. Chemotherapy wiped out his old immune system and the stem cells were transplanted back to grow a new immune system. Before the stem cells are transplanted back, patients are defenseless against microbes. The procedure is therefore too risky to be offered to everyone with MS. Angie White went through her stem cell transplant one year ago. She has no regrets. "If I hadn't had the transplant, the way I look at it, I would probably have ended up in a wheelchair." It's too early to call Angie's case a success story, but Freedman is encouraged by what he sees. "So far, there's absolutely no sign that the disease has come back in any of these patients," said Freedman. "So the longer it goes that they don't show anything, the better the chances are that this is representative of a long standing remission. And that's what our goal is, long standing remission." Freedman is presenting his results this week at the American Academy of Neurology's annual meeting in Hawaii.
Written by CBC News Online staff

Rheum Dis Clin North Am 2003 Feb;29(1):123-43, vii
Role of endogenous retroviruses in autoimmune diseases.
Perl A.

Departments of Medicine and Microbiology and Immunology, College of Medicine, State University of New York Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA. perla@u...Endogenous retroviruses (ERVs) correspond to the integrated proviral form of infectious retroviruses that are trapped within the genome by mutations. Endogenous retroviruses represent a key molecular link between the host genome and infectious viral particles.

Proteins encoded by ERVs are recognized by antiviral immune responses and become targets of autoreactivity. Activation of ERVs, such as human ERV-K or a human T-cell lymphotropic virus-related endogenous sequence, may also mediate pathogenicity of Epstein-Barr virus. Endogenous retrovirus peptides can directly regulate immune responses. Thus, molecular mimicry and immunomodulation by ERVs may account for self-reactivity and abnormal T- and B-cell functions in autoimmune disorders.

PMID: 12635504 [PubMed - in process]


Biologically Active Thymus Proteins plus Zinc
Balances Immune System Function
By, Daniel Clark M.D.

Immune Dysfunction:

Dysfunction of the Immune System affects about 65 million Americans. These dysfunctions manifest themselves in disorders such as Chronic Allergies and Respiratory problems, Arthritis, Diabetes, Lupus Erythematosus and Chronic Viral infections to name a few. The cost in terms of lost time at work, cost of related health care and diminished quality of life cannot be accurately estimated. However, everyone agrees that the costs are enormous. A good deal of the time and money related to Immune Dysfunction is actually spent treating the disorders rather than directly approaching the underlying cause itself.

Immune Dysfunction is likely the result of a combination of assaults on the immune system. Generally there is immune suppression then infection followed by treatment of the infection. If immune function is not restored, the initial infection may not resolve, or it may be followed by another infection eventually overwhelming the immune system causing it to overreact and under-react simultaneously. This is classic Immune Dysfunction, a patient with multiple low-grade infections and autoimmune disorders at the same time. Direct immune stimulation may exacerbate the autoimmune disorders, while treating autoimmune disorders may suppress immunity and allow infection to proliferate.

The Thymus Gland
The “brain” of the immune system is the thymus gland. It lies just beneath the breastbone and is responsible for producing perhaps dozens of different polypeptides that “program” lymphocyte progenitors. Lymphocytes are born in the bone marrow; some receive their programming in the bone marrow and are referred to as B-lymphocytes. Others migrate to the thymus gland to mature by contacting the thymic proteins and are referred to as T-lymphocytes. The T-lymphocytes display receptor sites on their surface that correspond to transmitter sites on the surface of the various thymic proteins. When the appropriate T-lymphocyte contacts its corresponding protein, the transmitter fits into the receptor (much like a key fits into a lock) and the lymphocyte is now ready to perform its specific function or is otherwise immune-competent.

There are two main types of T-lymphocytes. These are the T-4 (CD4) helper, and the T-8 (CD8) that further differentiate into killer and suppressor types. Helper cells not only induce killer and suppressor cells but also induce B-lymphocytes, and macrophages. Killer cells do just that, kill. When they are immune-competent they have the ability to recognize deviant cells such as tumor cells and the body’s own cells that are virally infected. Once recognized, the killer cell attacks. Sometimes killer cells overreact by attacking self-tissue (auto-immune disease) but if immune-competent suppressor cells are present, they intervene and stop the attack. Thus when the system is functioning properly the thymus produces proteins that “program” T-lymphocytes that start and stop immune response. Due to genetic flaw, trauma, stress, disease, exposure to toxic substances and/or inevitably the aging process, the thymus ceases to produce its proteins in the proper quantity or combinations to maintain immune balance.

Supplementation with Thymic Proteins
The use of thymic extracts has been well studied. There is a substantial body of clinical evidence that indicates the use of thymus is effective in the treatment of a number of diseases and disorders. Chronic viral infections, different types of cancers, and some auto-immune disorders are a few that I will discuss here.

Double-blind studies reveal that thymus extracts are able to eliminate viral infection; and continued use over one year reduces the number of recurrent infections. Additionally, patients in the studies show improved immune parameters1. In cancer patients, the primary indication for thymus use is for the treatment of lymphopenia/leukopenia caused by chemotherapy and radiation treatments. The effect is to prevent or at least mitigate the dramatic drop in white blood cell levels and to restore counts more quickly in cases where they do drop. The net result of patients taking thymus are that they are more often able to complete their treatment and with reduced side effects than in patients who do not take thymus2,3. Autoimmune disorders are immune dysfunction where the bodies’ own defense mechanisms are attacking self-tissue. Rheumatoid Arthritis, Lupus, and Scleroderma are classic disorders caused by increased antibody formation brought on by a high T-helper/T-suppressor ratio. A clinical study in Rheumatoid Arthritis patients revealed thatthymus extract use normalized their T-helper/T-suppressor ratios in three months2. Thymus is also indicated for the treatment of Hepatitis C, AIDS, Chronic Fatigue, Cold and Flu, Lupus Erythematosis, Type II Diabetes and Scleroderma. Studies are presently being conducted  for the treatment of Hepatitis C.

Another area of recent study for the application of thymus products has to do with the role lymphocytes play in periodontal disease. The first line of defense against bacterial plaque is neutrophils. Neutrophils are depressed in people susceptible to periodontal disease such as diabetics and the geriatric population. Lymphocytes promote neutrophil growth and thymus proteins promote lymphocyte growth. Lymphocytes therefore play a major role in prevention and resolution of periodontal disease10,11. Volumes of scientific data exist now to support the use of thymus products for immune suppression and immune dysfunction. There is precious little data however suggesting which specific thymus product is most effective.

Which Thymus Products are Best?
There are a variety of thymus products available from raw thymus tissue to highly purified thymus proteins and many thymus extracts in between. Thymus proteins are produced in the thymic epithelium and range in size from probably around 10,000 Dalton to perhaps over 50,000 Dalton. Whether large or small, proteins are complex molecules that can beeasily damaged (de-natured) or changed.  Changes in the protein molecule can bear directlyon its biological activity and therefore its ability to “program” T-lymphocytes. Therefore the manner in which the thymus product is handled and administered will bear directly upon how much benefit the patient experiences from using it.

Typical thymic extracts are composed of ground up thymus tissue, which is then freeze-dried and encapsulated to be swallowed and absorbed in the gastrointestinal tract. There are also liquid thymus extract drops that are takensublingually and a few products of freeze-dried purified thymus protein that is also administered sublingually.

My experience has taught me that the purified thymus protein administered  sublingually is the most effective. I have recently been testing a thymic compound called BioProtein+PlusTM that contains purified biologically active thymus proteins ranging in atomic size from 10,000 to 50,000 Dalton plus Zinc Gluconate.

The Role of Zinc
DNA makes RNA, which in turn makes proteins. Proteins drive biological function. Trace minerals work as catalysts or activators in enzyme complexes and influence reactivity and stability of protein configurations. Zinc has anti-oxidant properties and serves a vital role in many immune functions. Studies have shown that Zinc must be present for lymphocyte maturation and is a lymphocyte mitogen. Additionally, zinc is a necessary co-factor in activation of serum thymic factor5,6. Zinc Gluconate has been clinically proven to reduce the duration of the common cold by an average of 7 days7,8.

Zinc may also have some anti-aging benefits. An important study of zinc supplementation in elderly patients resulted in increased numbers of T-cells and enhanced cell-mediated immune responses9.

Our testing indicates that BioProtein+PlusTM works to regulate the T-helper/T-killer/T-suppressor interaction resulting in normalization of immune response. Our experience is consistent with clinical studies conducted with other thymus products. The quality of our results are due to the combination of biologically active purified thymus proteins contained in BioProtein+PlusTM working synergistically with the zinc gluconate to induce immune regulation.

A Unique Thymic Compound
BioProtein+PlusTM is a proprietary formula produced by the original manufacturer of BioPro Thymic Protein A. The thymus used in its manufacture comes from dairies in the US that only produce certified raw dairy products. It is certified free of microorganisms and BSE. The proteins are purified efficiently by the most up to date assay techniques while taking great care to maintain the proteins’ biological activity. They are then lyophilized to maintain their long-term stability.

The zinc gluconate used in the manufacture of BioProtein+PlusTM is of the highest quality available. Once freeze-dried, the purified thymus proteins and the zinc gluconate are triturated into a base of maltodextrin and packaged in doses containing about 400 mg of product each.

It is recommended by the manufacturer to be taken as a once per day supplement. Just as with BioPro Thymic Protein A, we have not seen any adverse side effects. On some occasions a health care professional may recommend more than one per day. As with other zinc products, toxicity does not occur unless a person takes over 150 mg of zinc per day for more than two weeks. BioProtein+PlusTM contains 10 mg of zinc per dose.

There are no known contraindications but BioProtein+PlusTM is likely to be less effective for people using steroidal medications.

Clinical Observations
As of this writing two clinical trials have begun using BioProtein+Plus TM. One trial is being conducted on subjects with Hepatitis C, the end point being to reduce viral load, normalize ALT, AST and increase general well being. The second trial is on Lymphopenia caused by chemotherapy toxicity. The following are observations made of individuals from these two trials:

Hepatitis C
Lew is a male age 46 who began using BioProtein+Plus TM in February 2000. Since that time to June, 2000, using one packet per day and no other treatment, he has seen his Quantitive viral count drop from 39,500 to 10,000, AST from 89 to 39, and ALT from 146 to 50. His energy level has improved and he sleeps better.

Chemotherapy Toxicity
Ethel began Taxol treatment for breast cancer in December 1999. She began using three packets of BioProtein+Plus TM per day when she began treatment. As of mid-July, 2000 she has received 8 rounds of Taxol. Throughout her treatment her blood parameters have remained in the normal range except her lymphocyte count dropped below normal for six weeks A Mature Lymphocyte Attacks a Tumor Cell from mid-March to the end of April. She completed her Taxol treatment without interruption.

Brief reports from health care professionals:
Kathryn, an acupuncturist in the state of Florida, has found the new BioProtein+Plus to be very effective at reducing viral load on her Hepatitis C patients referred to her by an Internist for acupuncture treatments. Michael, an acupuncturist also in the state of Florida, has found the new BioProtein+Plus effective in balancing immune function for a number of patients with autoimmune disorders.

Denise and Luby Chambul, D.C. of Nashville, Tennessee have used the BioProtein+Plus in Hepatitis C patients with effective reduction of viral load.

Dr. Herbert Warren of Alternative Health Concepts reports: I have been dispensing BioPro Thymic Protein A for over 4 years, to clients with a variety of health problems ranging form simple immune dysfunction to severe debilitating diseases like; Chronic Fatigue, Hepatitis C, severe Lymphopenia, and Cancer. In the vast majority of cases (90%), I have seen positive health benefits when the product was taken as recommended.

Since being introduced to the “new generation” product, BioProtein+Plus, I have observed the same extraordinary health benefits previously experienced with the aforementioned product and in several cases a more natural or complete immune regulation response has been observed, with out the “inflammatory flare”sometimes seen with BioPro. I can only surmise this is because of the more balanced and complete formulation of purified thymus proteins coupled with the zinc found in BioProtein+Plus.

I feel both products are phenomenal in enhancing the immune response, however, because of the smooth immune modulation and the cost differential between the two products, I prefer BioProtein+plus, as the supplement of choice to fully restore the cell mediated immunity so necessary for a healthy life.

Nothing teaches and convinces like one’s own experience. The author’s own observations and experience as well as other health care professionals is that BioProtein+PlusTM is an excellent tool in the battle against immune dysfunction. If you are a person who suffers with chronic viral infection while at the same time dealing with autoimmune disorder, ask your health professional about this product. If you are a health professional looking for an effective and cost-effective tool to recommend your clients, consider trying this product and experience it for yourself.

Riocchi A, Borella E, Riva E. et al. A double blind clinical trial for the evaluation of the therapeutic effectiveness of a calf thymus derivative in children with recurrent repiratory infection. Thymus 1986; 8: 831-839.
Kouttab NM, Prada M., Cazzola P. Thymomodulim. Biological properties and  clinical applications. Med Oncol Tumor Pharmacother 1989; 6: 5-9.
Kang SD, Lee B H, Yand JH, Lee CY. The effects of calf-thymus extract on recovery of bone marrow function in anticancer chemotherapy. New Med J (Korea) 1985; 28: 11-15.
Cazzola P, Mazzanti P, Bossi G. In vivo modulation effect of a calf thymus acid lysate on human T Lymphocyte subsets and CD4+/CD8+ ratio in the course of different diseases. Curr Ther Res 1987; 42: 1011-1017.
Eaterbrook-Smith S. Activation of the binding of C1q to immune complexes by zinc. FEBS Lett 1983; 162: 117-119.
Hadden JW. The treatment of zinc deficiency is an immunotherapy. Int J Immunopharmac 1995; 17: 697-701.
Eby GA, Davis DR, Halcomb WW. Reduction in duration of common colds by zinc gluconate lozenges in a double-blind study. Antimicrob Agents Chemother 1984;25: 20-24.
Mossad SB, Macnin ML, Medendorp SV et al. Zinc gluconate lozenges for treating the common cold. A randomized, double blind, placebo-controlled study.Annals Intern Med 1996; 125: 81-88.
Gershwin M, beach R, Hurley L. Trace metals, aging and immunity. J Am Ger Soc 1983; 31: 374-378.
Carranza F. Glickman’s clinical peridontology. Philadelphia, PA: WB Saunders.1984.
Page R, Schroeder H. Current status of the host response in chronic marginal periodontis. J Periodontal 1981; 53: 477-491.

About the Author:
Dr. Daniel Clark is a noted researcher and lecturer in the field of alternative medicines. He is located in Melbourne FL.


Endometriosis Linked to Autoimmune and Other Chronic Diseases Including Chronic Fatigue Syndrome & Fibromyalgia
By Laurie Barclay, M.D.

A cross-sectional survey reported in the Sept.  27 (2002) issue of Human Reproduction showed that women with endometriosis have higher rates of autoimmune and other chronic diseases than do women in the general U.S.  population.

"Women with endometriosis frequently suffer from autoimmune inflammatory diseases, hypothyroidism, fibromyalgia (FM), chronic fatigue syndrome (CFS), allergies and asthma," lead author Ninet Sinaii, from the National Institute of Child Health and Human Development in Bethesda, Maryland, says in a news release.  "These findings also suggest a strong association between endometriosis and autoimmune disorders and indicate the need to consider the co-existence of other conditions in women with endometriosis."

In this population-based survey of 3,680 members of the Endometriosis Association, all had surgically diagnosed endometriosis, 90% were of reproductive age, 66% had a positive family history for diagnosed or suspected endometriosis, and 20% had more than one other chronic disease.  Nearly one-third of those with coexisting diseases also had been diagnosed with either FM or CFS, and some of these women also had other autoimmune or endocrine disease.

Compared with expected rates in the general population of U.S.  women, women in this survey had increased rates of chronic disease.  CFS was more than a hundred times more common (4.60% vs.  0.03%, P<.0001), hypothyroidism seven times more common (9.6% vs.  1.5%, P<.0001), and FM was nearly twice as common (5.9% vs.  3.4%, P<.0001).

Women with endometriosis also had higher than expected rates of autoimmune inflammatory diseases including systemic lupus erythematosus, Sjögren's syndrome, and rheumatoid arthritis, as well as multiple sclerosis.  Allergies occurred in 61% (vs.  18%; P<.001) and asthma in 12% (vs.  5%; P<.001) of survey subjects overall.  Of those subjects who also had FM or CFS, 88% had allergies (P<.001) and 25% had asthma (P<.001).

"As well as finding an increased prevalence of this wide range of diseases and conditions among women with endometriosis, we found that they reported significant pain and disability and, very worryingly, that there was typically a 10-year delay between the onset of pelvic pain and diagnosis," Sinaii says.

Potential study limitations included the subjects being relatively young, predominantly white, well-educated, and members of a support group.  However, sensitivity analysis confirmed that even if chronic disease prevalence rates were underestimated in the general population and overestimated in the survey, the rates reported in women with endometriosis were still significantly higher.

"Since women appear to develop symptoms shortly after the onset of their periods and are not diagnosed for years, we don't know whether endometriosis actually occurs at menarche as others have reported or whether it develops over time," senior author Pamela Stratton says.  "It's also unclear whether early treatment could prevent chronic pelvic pain from taking hold.  It is vital therefore that attempts should be made to diagnose and treat endometriosis in adolescents."

Hum Reprod.  2002;17(10):2715-2724
Reviewed by Gary D.  Vogin, M.D.
Source: WebMD


New Study Shows MMR/Autism Link

[From Autism Research Campaign For Health 23 June 2003. See referenced abstract below “Elevated levels of measles antibodies in children with autism” by Vijendra K. Singh PhD*, and Ryan L. Jensen BS.]

A new study, published in Pediatric Neurology, Vol. 28, No. 4, is expected to show that MMR and autism are linked, despite the denials of the UK Department of Health and the recent court judgment that ordered two girls to receive the controversial MMR vaccine. World-renowned autism researcher Dr. Vijendra Singh, at the Utah State University, and fellow-researcher Ryan Jensen have announced that their latest study,” Elevated Levels of Measles Antibodies in Children with Autism”, points directly to an MMR/autism link. Singh and Jensen analysed samples from 52 autistic children, all of whom had had the MMR vaccination, and 30 normal children, plus a further 15 siblings of autistic children.

They showed that measles antibody levels, a sign of an immune reaction to measles virus, were significantly greater in children with autism compared with the non-autistic children. Levels of mumps and rubella antibodies were not different from the non-autistic children. Strikingly, they found that 43 out of the 52 (83%) of the autistic children had antibodies to the measles vaccine virus. None of the 30 normal children, and none of the 15 siblings, had these antibodies. Singh and Jensen have concluded that the antibody results show that many autistic children have suffered an abnormal response to the measles element of the MMR vaccine, causing them to develop "inappropriate"  antibodies.

Singh and Jensen were testing a hypothesis that, as viruses are common trigger agents for autoimmune diseases, where the human body attacks itself, then autism could involve a virus-induced autoimmune response, in turn leading to autism. The study looked at 88 autistic children, all of whom had a firm diagnosis of autism. Not all children were tested for all the three viruses, of measles, mumps or rubella. In those children tested, the level of mumps or rubella antibodies did not attain statistical significance, leaving the researchers to focus upon the measles element of MMR. None of the autistic children had any history of measles rash or wild-type natural measles infection.

This points to the source of the measles antibody as being vaccine strain. The researchers are undertaking further study work on this crucial aspect. If the new research by Singh and Jensen is correct, then it backs up the claims of many families who have reported that their children became autistic after MMR. It also confirms the validity of the1998 study by Dr. Andrew Wakefield and other researchers in the UK, and a number of other studies published since that time. Over 1,000 cases of autism following MMR are being brought before the High Court in London in April 2004. If the claims are upheld, it will have dramatic implications for vaccine policy worldwide, and will throw a spotlight on the way vaccines are licensed and regulated.

ARCH - Autism Research Campaign for Health - is a group of parents campaigning for more research into the causes and treatment of autism. It was set up in response to the departure of Dr Andrew Wakefield from the Royal Free Hospital – which ARCH viewed as a sign that medical scientists were no longer free to follow their own lines of enquiry. We are profoundly worried that medical science is now dictated by government, the medical establishment and the pharmaceutical industry who between them control the vast sums of research money and determine which topics are legitimate research and which are not. This state of affairs is unacceptable to the growing number of children and parents who must live with the painful consequences of autism, and with the lack of research into the alarming increase in the prevalence of autism in many countries across the world. ARCH believes that there is mounting evidence that suggests MMR is unsafe. It calls on the UK Government to fund clinical research into the effects of MMR vaccine on the immune system of autistic children and its role in the onset of regressive autism, epilepsy and bowel disease. Visit ARCH on

Clinical Immunology
Vol. 100, No. 3, September, pp. 355-361, 2001
available online at

Infection of Human B Lymphocytes with MMR Vaccine Induces IgE Class

Farhad Imani and Kelly E. Kehoe

Division of Clinical Immunology, Department of Medicine, The John Hopkins University School of Medicine, Asthma and Allerrgy Center, 5501 Hopkins Bayview Circle, Baltimore, Maryland 21224
Correspondence should be addressed. E-mail: fimani@m...

Circulating immunoglobulin E (IgE) is one of the characteristics of human allergic diseases including allergic asthma. We recently showed that infection of human B cells with rhinovirus or measles virus could lead to the initial steps of IgE class switching. Since many viral vaccines are live viruses, we speculated that live virus vaccines may also induce IgE class switching in human B cells. To examine this possibility, we selected the commonly used live attenuated measles mumps rubella (MMR) vaccine. Here, we show that infection of a human IgM+ B cell line with MMR resulted in the expression of germline e transcript. In addition, infection of freshly prepared human PBLs with this vaccine resulted in the expression of mature IgE mRNA transcript. Our data suggest that a potential side effect of vaccination with live attentuated viruses may be an increase in the expression of IgE.


Inhibitory Signal Override Increases Susceptibility to Mercury-Induced Autoimmunity 1

Yan Zheng and Marc Monestier2 Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, PA 19140

After exposure to subtoxic doses of heavy metals such as mercury, H-2s mice develop an autoimmune syndrome consisting of the rapid production of IgG autoantibodies that are highly specific for nucleolar autoantigens and a polyclonal increase in serum IgG1 and IgE. In this study, we explore the role of two inhibitory immunoreceptors, CTLA-4 and FcRIIB, in the regulation of mercury-induced autoimmunity. In susceptible mice treated with mercuric chloride (HgCl2), administration of a blocking anti-CTLA-4 Ab resulted in a further increase in anti-nucleolar autoantibodies and in total serum IgG1 levels. Furthermore, in some DBA/2 mice, which are normally resistant to heavy metal-induced autoimmunity, anti-CTLA-4 treatment leads to the production of anti-nucleolar Abs, thereby overcoming the genetic restriction of the disease. In mice deficient for the FcRIIB, HgCl2 administration did not trigger autoantibody production, but resulted in an increase in IgE serum levels. Taken together, these results indicate that different inhibitory mechanisms regulate various manifestations of this autoimmune syndrome.

Vaccine ingredients could trigger autoimmune disease
6 August 2003 15:00 GMTby Helen Dell

Mineral oils that are common components of vaccines induce the production of pathogenic autoantibodies and an inflammatory immune response when injected into mice, report US researchers. They suggest that these oils could be inducing autoimmunity in susceptible people. The oils are used as adjuvants in vaccines - substances that enhance the immunogenicity of an antigen. It has been known for some time that some mineral oils can induce autoimmunity in the
form of arthritis, indeed they are injected into mice to produce animal models for arthritis.

Now, Minoru Satoh, research associate professor at the Division of Rheumatology and Clinical Immunology at the University of Florida, and colleagues have examined at the oils' effect in another autoimmune disease - systemic lupus erythematosus (SLE).

SLE is a systemic autoimmune disease characterized by fever, weakness, arthritis, skin rashes, pleurisy and kidney dysfunction. Individuals produce autoantibodies to a wide array of tissue antigens, including DNA, histones, platelets, leucocytes, and many others.

Satoh's team injected mice with the most common adjuvants used in human and veterinary vaccines, incomplete Freund's adjuvant (IFA) and squalene, and tested to see whether SLE-specific antibodies were produced. They found that up to a quarter of the mice produced autoantibodies that are SLE-specific. "The induction of autoantibodies was highly selective," they note. The ability of the oils to produce autoantibodies appears to correlate with the production of the inflammatory mediator molecules IL-12, IL-6 and TNF-alpha.

"I think this is a very significant finding because there is a possibility that vaccination in animal or human can induce lupus autoantibodies in susceptible individuals," said Satoh. His team are now testing the effects of medicinal mineral oil and other adjuvant components. "Hopefully, we can find some safe [mineral oil] that can be used as adjuvant but doesn't induce lupus autoantibodies," he said.

The researchers are also beginning to look for genetic factors that might influence susceptibility to SLE autoantibody production. They have tested 25 common laboratory strains of mice, each of which has a slightly different, well-defined genotype. However, mice from all the strains produced the SLE autoantibodies after injection with mineral oils, making it difficult to separate out the genes that might underlie susceptibility.

Thomas Aune, Associate Professor of Medicine at Vanderbilt University in Nashville, Tennessee, has been looking at gene expression patterns in people with autoimmune disease to see how they differ from patterns in people without disease. He is cautious about the new results. Environmental insults that are proposed to cause autoimmunity have waxed and waned in popularity over the years, he says, but none have really stood the test of time.

Induction of lupus autoantibodies by adjuvants.

Satoh M, Kuroda Y, Yoshida H, Behney KM, Mizutani A, Akaogi J, Nacionales DC, Lorenson TD, Rosenbauer RJ, Reeves WH.

Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Florida, P.O. Box 100221, 1600 SW Archer Road, 32610-0221, Gainesville, FL, USA

Exposure to the hydrocarbon oil pristane induces lupus specific autoantibodies in non-autoimmune mice. We investigated whether the capacity to induce lupus-like autoimmunity is a unique property of pristane or is shared by other adjuvant oils.

Seven groups of 3-month-old female BALB/cJ mice received a single intraperitoneal injection of pristane, squalene (used in the adjuvant MF59), incomplete Freund's adjuvant (IFA), three different medicinal mineral oils, or saline, respectively.

Serum autoantibodies and peritoneal cytokine production were measured. In addition to pristane, the mineral oil Bayol F (IFA) and the endogenous hydrocarbon squalene both induced anti-nRNP/Sm and -Su autoantibodies (20% and 25% of mice, respectively). All of these hydrocarbons had prolonged effects on cytokine production by peritoneal APCs. However, high levels of IL-6, IL-12, and TNFalpha production 2-3 months after intraperitoneal injection appeared to be associated with the ability to induce lupus autoantibodies.

The ability to induce lupus autoantibodies is shared by several hydrocarbons and is not unique to pristane. It correlates with stimulation of the production of IL-12 and other cytokines, suggesting a relationship with a hydrocarbon's adjuvanticity. The potential to induce autoimmunity may complicate the use of oil adjuvants in human and veterinary vaccines.


‘Tonight with Trevor McDonald’
Monday, March 17, 2003 on ITV1 at 8pm

Military anthrax vaccine contains a potentially dangerous substance, which the Ministry of Defence has previously denied, according to a special TV investigation. ITV1’s Tonight with Trevor McDonald programme this evening [Monday] at 8pm, has obtained MOD Anthrax vaccine samples which tested positive for Squalene – an agent that has not been granted a licence for use in drugs.

The revelation comes as more than half of British service people heading to the Gulf have refused a voluntary Anthrax vaccination, according to the Liberal Democrats.  Last week Defence spokesman Paul Keetch MP said that of the 16,538 service personnel offered the jabs only 8,103 accepted.
The capsules containing the Anthrax vaccine were washed up on a beach in Bridport, Dorset in January. The MOD are currently investigating the samples but have not been able to discover how the vaccines got there.

The Tonight team acquired some of the Bridport capsules, which were tested in a government-accredited laboratory SAL based in Manchester.  The results showed that the vaccine contains 36 parts of Squalene per billion.

Professor Malcolm Hooper, a scientist who sits on two independent committees set up the government to investigate illnesses of Gulf war veterans, tells the programme that – even in miniscule amounts - Squalene can generate Auto Immune Disease.

“Squalene can generate antibodies which can result in Auto Immune Disease,” says Professor Hooper.  “So they attack our own bodies with our own immune system and this can effect nerve, it can effect cardiac tissue, it can effect skin… So Squalene is a no, no.  It’s not been recommended for use in human vaccines, its been tried in a lot of animal experiments.

“Squalene is bad news but we know some UK veterans from the first Gulf war had got Squalene anti-bodies in their blood and that was surprising because again it was said [by the MOD] there was no Squalene in any of the vaccines that our people had been given from the UK sources.”

Professor Hooper says that even minute traces of Squalene could have serious side effects: “You don’t need very much, the immune system is extremely sensitive at that sort of level we’re talking about… An almugram is a millionth of a gram, we’re talking about a thousand billions to the gram…the body does respond to these very tiny amounts of some substances and so I am really concerned.”

The MOD has consistently denied that the Anthrax vaccine contains Squalene and their own tests did not reveal any. They say they’re still waiting for the results of research into whether any of their vaccines from Operation Desert Storm made British troops sick.

The Department of Health – who encompass the Medicines Control Agency – tells Tonight that Squalene has never been included in the UK licensed Anthrax vaccine and that Squalene is not used in the manufacture of the vaccine.

But Dr Pam Asa who is affiliated to the Tulane Medical School in Louisiana, USA, believes that the programme’s findings are highly significant and mean that the current Anthrax vaccine may be potentially dangerous.  Dr Asa has tested more than 300 former US military personnel who were given vaccinations before the 1991 Gulf War.

Says Dr Asa:  “It gave us the opportunity to have the vaccine analysed for content, to determine if there was Squalene in it and this was our first opportunity.  It was a treasure, because denials are one thing but when you actually have it chemically analysed you get to the truth.”

Although Squalene occurs naturally in the body, scientific research has shown that when it is injected it could have a different effect.  “We eat a number of things that we would not inject in our bodies,” says Dr Asa.  The fact is when we ingest through our mouths…it goes into our bodies in a way that our body accepts it and uses it for nutritional purposes.  When we inject it, it goes into the lymphatic system and is processed in a very different way and our body recognises injected Squalene as a foreign material that it needs to react to, immunologically.”

“I have a patient who got ten parts [of Squalene] per billion and he has gone on to develop rheumatoid arthritis, he has a very high level of anti Squalene antibodies.  He received two Anthrax shots that contain Squalene, determined by the Food and Drug Administration, and then went on to develop Rheumatoid Arthritis.  Others in his group his unit have developed Lupus in their mass and Auto Immune Disease.

“I’m afraid we’ll see people developing the same diseases that I’ve seen from the 1998 - 2000 group, which is again Lupus, MS, Rheumatoid Arthritis and ALS.”

As British troops await orders in the Gulf, Tonight speaks to Ray Bristow, a Gulf war veteran from 1991 who believes that the drugs and vaccines given to him are responsible for over 30 conditions he has now been diagnosed with - including fits, memory loss, incontinence and chronic fatigue.

“When I went out to the Gulf I was obviously very fit, otherwise they wouldn’t let me go,” says Ray.  “I used to run marathons for charities as a hobby. I’d run fifty miles a week.  When I first came back, my health started to deteriorate.  I remember sitting on the end of the bed with my head in my hands thinking I was going mad.  I couldn’t understand what was happening… I’ve had my dignity stripped from me and it should never have happened.”

The former army medic says that the British vaccination programme in Operation Desert Storm  was a disgrace and lessons should be learnt: “I would say it was a very shambolic way of vaccinating people.  Nobody knew what was being given.  Who knows if they were giving the correct dosages?  It was a complete disgrace; I never witnessed anything like it in my twenty years in the health services.

“For me its too late [but] if they rush the vaccine programme again you’re going to get lots of troops [who] will come back sick in ten years time.  If they can wait for men and materials to be deployed, they can wait for the ships to get there with the tanks, then surely they can wait an extra few weeks so they can initiate the vaccine programme in a proper manner.”

Shaun Rusling, chairman of the National Gulf Veterans and Families Association, says that Tonight’s findings are highly significant: “The presence of Squalene in the Anthrax vaccine is extremely significant.  It would not surprise me if the Bridport sample was thrown overboard by outgoing troops to Iraq who know what the vaccine contains.”

Minister of Defence, Dr Lewis Moonie, has previously stated that tests might reveal antibodies for Squalene in war veterans but has categorically denied it came from any Anthrax vaccination.  He has also stated that, “There is no such thing as Gulf war syndrome – they’re a collection of illnesses which don’t fit any particular pattern”.

The Tonight programme has presented its findings to the MOD and is awaiting a response.

NOTES TO EDITORS:   Please credit ITV1’s Tonight with Trevor McDonald at 8pm Monday, if any of this material is used


Vaccination and autoimmune disease: what is the evidence?
David C Wraith, Michel Goldman, Paul-Henri Lambert

As many as one in 20 people in Europe and North America have some form of autoimmune disease. These diseases arise in genetically predisposed individuals but require an environmental trigger. Of the many potential environmental factors, infections are the most likely cause. Microbial antigens can induce cross-reactive immune responses against self-antigens, whereas infections can non-specifically enhance their presentation to the immune system. The immune system uses fail-safe mechanisms to suppress infection-associated tissue damage and thus limits autoimmune responses. The association between infection and autoimmune disease has, however, stimulated a debate as to whether such diseases might also be triggered by vaccines. Indeed there are numerous claims and counter claims relating to such a risk. Here we review the mechanisms involved in the  induction of autoimmunity and assess the implications for vaccination in human beings.
Published online June 3, 2003


Pigment Cell Research
Volume 16 Issue 5 Page 589 - October 2003

The Epidemiology and Genetics of Generalized Vitiligo
R. Spritz1, P. Fain1 and D. Bennett2
Generalized vitiligo, in which white patches of skin and hair due to melanocyte death, is among the most common autoimmune diseases, occurring in 1/200 people worldwide. To better understand the disorder's epidemiology, and to ascertain families for genetic analysis, we surveyed  13,000 probands, finding that, in a subset of families, generalized vitiligo, autoimmune thyroid disease, pernicious anemia, lupus Addison's disease, adult-onset autoimmune diabetes, and perhaps inflammatory bowel disease are highly associated, both in vitiligo patients and their relatives. We carried out genome-wide linkage analysis of  90 families with multiple family members with generalized vitiligo, detecting a highly significant linkage on chromosome 1p, designated AIS1, as well as at least 7 suggestive linkage signals located elsewhere in the genome. None of these potential vitiligo susceptibility loci correspond to the positions of candidate genes that have been suggested previously. Stratifying these multiplex vitiligo families by presence or absence of the other vitiligo-associated autoimmune diseases demonstrated that AIS1 is genetically linked to the vitiligo-associated autoimmune disease constellation, but not to vitiligo alone, suggesting that there are at least two forms of generalized vitiligo. A 2-locus linkage analysis of one large family indicated that AIS1 may interact with another locus on chromosome 6 to cause autoimmune thyroid disease. We also carried out linkage analysis for age of onset for vitiligo, finding strong QTLs on chromosomes 1 and 2 that do not correspond to any of the linkage signals for vitiligo susceptibility itself. AIS1 maps to a 7.4 Mb interval on chromosome 1p which contains only 30 genes, including a particularly attractive positional biological candidate gene. DNA sequence analysis and SNP segregation and association studies indicate that this candidate may be involved in the pathogenesis of generalized vitiligo.

Tue Sep 2 15:04:42 2003 Pacific Time

      Study Suggests Low-Dose Mercury Accelerates Autoimmune Disease  

BALTIMORE, Sept. 2 (AScribe Newswire) -- A study conducted at the University of Maryland School of Medicine finds that exposure to low levels of mercury can speed up and worsen the symptoms of an induced lupus-like disease in mice, even when the exposure occurs before the development of the disease. The researchers say if this relationship were shown to be true in humans, it would redefine the association between mercury exposure and the autoimmune disease lupus. Their study, the first to connect low-level mercury exposure to the severity of lupus in mice after they develop the disease, appears in the August 2003 edition of Environmental Health Perspectives, published by the National Institute of Environmental Health Sciences, part of the National Institutes of Health.

       The lead investigator of the study, Charles S. Via, M.D., professor of medicine, microbiology and immunology at the University of Maryland School of Medicine, says previous studies have found that mercury exposure in animals can exacerbate pre-existing autoimmune disease and even induce autoimmune disease in susceptible animals.

       "Our study takes the link further by demonstrating that exposure to mercury prior to the induction of an autoimmune disease in mice significantly worsens the severity of that disease after it develops," says Dr. Via, who is also a rheumatologist at the University of Maryland Medical Center.

       Scientists are uncertain about the impact of mercury exposure on humans. "There is considerable concern over potential neurotoxic effects associated with current levels of human exposure to mercury," says study co-author, Ellen K. Silbergeld, Ph.D., a professor of Environmental Health Sciences at the Johns Hopkins Bloomberg School of Public Health, who formerly worked at the University of Maryland School of Medicine. "These results suggest that we should examine the immune system as a target of mercury toxicity in humans."

       One step in that direction involves using special mouse strains to study the links between mercury and autoimmune disease. In one strain, the mice are susceptible to mercury-induced autoimmune disease. Another strain of mice develops an autoimmune disease that is similar to lupus.

       In this study, healthy mice that were not genetically susceptible to mercury-induced autoimmune disease were given injections of low-dose inorganic mercury over the course of two weeks. The levels of mercury and the length of exposure chosen were much lower than the range commonly used in mouse studies of mercury toxicity. Five days later, the mice were given cells from the lupus-inclined mouse strain to induce lupus-like chronic graft-versus-host disease, a well-established mouse model of acquired autoimmunity.

       Dr. Via says the results surprised him. Mercury exposure accelerated the deaths of the lupus-induced mice and sped up the course of a kidney disease associated with lupus. Further, antibodies, or markers characteristic of lupus-like autoimmunity were significantly elevated in the mice that had been pretreated with mercury. "Our findings suggest that low-level mercury exposure does not cause lupus," says Dr. Via. "Lupus is clearly multifactorial. You have to have a susceptible individual who has the appropriate environmental exposure. But our study clearly shows that mercury can act as a disease modifier for lupus. Exposure to mercury might either lower the threshold of susceptibility, or increase the severity of the disease."

       According to Dr. Via, the researchers have begun additional studies to determine whether subtle abnormalities remain after mercury clears from the body that may produce the modifications in lupus. "We can speculate about a lot of possible mechanisms, but we clearly need further study to determine exactly how mercury accelerates lupus," says Dr. Via.
       Lupus is a chronic disease that causes inflammation of connective tissue. The most common form of lupus affects exposed areas of the skin, while the more serious and potentially fatal form can affect many systems of the body including the kidneys. It is an autoimmune disorder, in which the immune system for unknown reasons attacks connective tissue as though it were foreign.

       Other members of the research team include Phuong Nguyen, B.S., Florin Niculescu, M.D., Ph.D., John C. Papadimitriou, M.D., Ph.D., and Dennis Hoover, Ph.D., all of the University of Maryland School of Medicine.


Infection with Mycobacterium bovis BCG Diverts Traffic of Myelin Oligodendroglial Glycoprotein
Autoantigen-Specific T Cells Away from the Central Nervous System and Ameliorates Experimental Autoimmune Encephalomyelitis.

Sewell DL, Reinke EK, Co DO, Hogan LH, Fritz RB, Sandor M, Fabry Z.

Department of Pathology and Laboratory Medicine, University of Wisconsin. Department of Microbiology, Medical College of Wisconsin, Milwaukee, Wisconsin.

Infectious agents have been proposed to influence susceptibility to autoimmune diseases such as multiple sclerosis. We induced a Th1-mediated central nervous system (CNS) autoimmune disease, experimental autoimmune encephalomyelitis (EAE) in mice with an ongoing infection with Mycobacterium bovis strain bacillus Calmette-Guerin (BCG) to study this possibility. C57BL/6 mice infected with live BCG for 6 weeks were immunized with myelin oligodendroglial glycoprotein peptide (MOG(35-55)) to induce EAE. The clinical severity of EAE was reduced in BCG-infected mice in a BCG dose-dependent manner. Inflammatory-cell infiltration and demyelination of the spinal cord were significantly lessened in BCG-infected animals compared with uninfected EAE controls. ELISPOT and gamma interferon intracellular cytokine analysis of the frequency of antigen-specific CD4(+) T cells in the CNS and in BCG-induced granulomas and adoptive transfer of MOG(35-55)-specific green fluorescent protein-expressing cells into BCG-infected animals indicated that nervous tissue-specific (MOG(35-55)) CD4(+) T cells accumulate in the BCG-induced granuloma sites. These data suggest a novel mechanism for infection-mediated modulation of autoimmunity. We demonstrate that redirected trafficking of activated  CNS antigen-specific CD4(+) T cells to local inflammatory sites induced by BCG infection modulates the initiation and progression of a Th1-mediated CNS autoimmune disease.

Naturally occurring anti-IFN{gamma} auto-antibody and severe infections with Mycobacterium cheloneae and Burkholderia cocovenenans.

Hoeflich C, Sabat R, Rosseau S, Temmesfeld B, Slevogt H, Docke WD, Gruetz G, Meisel C, Halle E, Goebel UB, Volk HD, Suttorp N.

Institute for Medical Immunology, University Hospital Charite, Humboldt University, Berlin, Germany.
Recently various genetic defects in IFNgamma mediated immunity have been described including mutations in the interferon-gamma receptor 1 (IFNgR1) and receptor 2 (IFNgR2), Stat1 and IL-12 receptor beta 1 (IL-12Rb1) and IL-12 p40 genes. These mutations are associated with the occurrence of severe infections with intracellular pathogens especially nontuberculous mycobacteria and vaccine-associated BCG. Here we report on a previously healthy adult patient primarilary presenting with severe infections with Burkholderia cocovenenans and subsequently Mycobacterium cheloneae. We found a strong inhibitory anti-IFNgamma activity in the patient's plasma and identified a high-affinity neutralizing anti-IFNgamma autoantibody. Unfortunately, the patient died due to severe sepsis before knowing the nature of the  inhibitory activity. The application of alternative therapeutic approaches such as IVIG or immunoadsorption may have been beneficial in this case. Screening for neutralizing anti-IFNgamma autoantibodies should supplement testing for IFN-gamma
and IL-12 pathway defects in patients with recurrent infections with intracellular pathogens, especially with NTM.

Ann N Y Acad Sci. 2003 Nov; 1005: 404-8. Related Articles, Links

Vaccinations may induce diabetes-related autoantibodies in one-year-old children.

Wahlberg J, Fredriksson J, Vaarala O, Ludvigsson J; Abis Study Group.

Division of Pediatrics, Department of Molecular and Clinical Medicine, Faculty of Health Sciences, Linkoping University, Linkoping, Sweden.

Vaccinations have been discussed as one among many environmental candidates contributing to the immune process that later may lead to type 1 diabetes. ABIS (All Babies in Southeast Sweden) is a prospective cohort study following a nonselected birth cohort of general population. In a randomly selected sample collection from 4400 children, GADA and IA-2A have been determined at the age of 1 year. The information on vaccinations was collected from questionnaires answered by the parents and was related to beta cell autoantibodies. When studying the induction of autoantibodies using the autoantibody level of 90th percentile as cutoff level, hemophilus influenza B (HIB) vaccination appeared to be a risk factor for IA-2A [OR 5.9 (CI 1.4-24.4; p = 0.01)] and for GADA [OR 3.4 (CI 1.1-10.8; p = 0.04)] in logistic regression analyses. Furthermore, the titers of IA-2A were significantly higher (p < 0.01 in Mann-Whitney test) in those children who had got HIB vaccination. When 99th percentile was used as cutoff to identify the children at risk of type 1 diabetes, BCG vaccination was associated with increased prevalence of IA-2A (p < 0.01). We conclude that HIB vaccination may have an unspecific stimulatory polyclonal effect increasing the production of GADA and IA-2A. This might be of importance under circumstances when the beta cell-related immune response is activated by other mechanisms.

PMID: 14679101 [PubMed - indexed for MEDLINE]


Toxicology. 2004 Mar 15;196(3):211-6.   Related Articles,Links 
Autoimmunity, environmental exposure and vaccination: is there a link?

Ravel G, Christ M, Horand F, Descotes J.

MDS Pharma Services, 69210 St Germain sur l'Arbresle, France.

Although the wide clinical experience shows that vaccines are generally safe, concern has been expressed for a causal link between vaccines and autoimmune diseases. Even though the mechanisms of autoimmunity are ill-elucidated, the role of pre-existing risk factors including genetic predisposition and environmental factors is largely accepted. The present study was undertaken to test the hypothesis that vaccines can promote autoimmunity in genetically-prone individuals when simultaneously exposed to a chemical known to induce autoimmune reactions. Female lupus-prone (NZB x NZW) F(1) mice were given 1 microg or 10 microg of a hepatitis B vaccine at 2-week intervals in conjunction with 40 microg of mercuric chloride three times per week for 6 weeks. A marked increase in serum IgG levels and a slight increase in anti-nuclear autoantibody (ANA) levels were seen in the mice given 10 microg of the vaccine plus mercuric chloride. No straightforward conclusion can be drawn from these results because of the extreme experimental conditions of this study. Nevertheless, the results tend to support the hypothesis that vaccination could enhance the risk of
autoimmunity in genetically susceptible individuals when exposed to certain environmental chemicals.

PMID: 15036747 [PubMed - in process]

Curr Opin Otolaryngol Head Neck Surg. 2004 Jun;12(3):223-231.   Links  
Vaccination and allergy.

Rottem M, Shoenfeld Y.

Division of Allergy and Clinical Immunology, Ha'Emek Medical Center, Afula, and Department of Medicine 'B' and Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, and Sackler Faculty of Medicine, Tel Aviv University, Israel.

PURPOSE OF REVIEW: Vaccines have had a major effect on controlling the spread of infectious diseases, but use of certain vaccines was linked to potential allergic and autoimmune side effects in healthy and often in certain high-risk populations. In this review the authors summarize the current knowledge of such risks.
RECENT FINDINGS: Immediate systemic allergic reactions after vaccination with commonly used vaccines are extremely rare. Use of certain vaccines was linked to potential allergic side effects in healthy and often in certain high-risk populations. The authors review the data on the risk associated with important vaccines including influenza, smallpox, pneumococcus, Japanese encephalitis, Bacille Calmette-Guerin, pertussis, and measles, mumps, and rubella. Two main components were identified as a source for allergic reactions in vaccines: gelatin and egg protein. There is growing interest in the potential interactions between infant vaccination and risk for development of atopic disease. In addition, there is concern that genetic risk for atopy influences capacity to respond to vaccination during infancy. There is no evidence that vaccinessuch as Bacille Calmette-Guerin; pertussis; influenza; measles, mumps, and rubella; or smallpox have an effect on the risk of the development of atopy later in life. Immunotherapy provides an efficacious and safe method for the treatment of allergic conditions by immunomodulation of the immune system. The possibility of vaccination triggering or unmasking autoimmunity in genetically susceptible individuals cannot be ruled out, but for the general population the risk-to-benefit ratio is overwhelmingly in favor of vaccinations.

Childhood vaccination remains an essential part of child health programs and should not be withheld, even from children predisposed to allergy. Vaccinations are safe, but special attention should be taken in high-risk individuals with anaphylactic reactions to foods, and in patients with autoimmune diseases.

PMID: 15167034 [PubMed - as supplied by publisher] 

Autism & Lymphocyte receptors

  Infections, toxic chemicals and dietary peptides binding to lymphocyte receptors and tissue enzymes are major instigators of autoimmunity in autism.
  Vojdani A, Pangborn JB, Vojdani E, Cooper EL.
  Lab.  Comparative Immunology, Dept.  Neurobiology, UCLA Medical Center, Los Angeles, CA, USA.
  Similar to many complex autoimmune diseases, genetic and environmental   factors including diet, infection and xenobiotics play a critical role in   the development of autism.  In this study, we postulated that infectious   agent antigens such as streptokinase, dietary peptides (gliadin and casein)  and ethyl mercury (xenobiotic) bind to different lymphocyte receptors and tissue enzyme (DPP IV or CD26).  We assessed this hypothesis first by measuring IgG, IgM and IgA antibodies against CD26, CD69, streptokinase (SK), gliadin and casein peptides and against ethyl mercury bound to human serum albumin in patients with autism.  A significant percentage of children with autism developed anti-SK, anti-gliadin and casein peptides and anti-ethyl mercury antibodies, concomitant with the appearance of anti-CD26 and anti-CD69 autoantibodies.  These antibodies are synthesized as a result of SK, gliadin, casein and ethyl mercury binding to CD26 and CD69, indicating that they are specific.  Immune absorption demonstrated that only specific antigens, like CD26, were capable of significantly reducing serum anti-CD26 levels.  However, for direct demonstration of SK,  gliadin, casein and ethyl mercury to CD26 or CD69, microtiter wells were  coated with CD26 or CD69 alone or in combination with SK, gliadin, casein  or ethyl mercury and then reacted with enzyme labeled rabbit anti-CD26 or anti-CD69.  Adding these molecules to CD26 or CD69 resulted in 28-86%  inhibition of CD26 or CD69 binding to anti-CD26 or anti-CD69  antibodies.  The highest % binding of these antigens or peptides to CD26 or  CD69 was attributed to SK and the lowest to casein peptides.  We, therefore, propose that bacterial antigens (SK), dietary peptides (gliadin, casein) and Thimerosal (ethyl mercury) in individuals with pre-disposing HLA molecules, bind to CD26 or CD69 and induce antibodies against these molecules.  In conclusion, this study is apparently the first to demonstrate that dietary peptides, bacterial toxins and xenobiotics bind to  lymphocyte receptors and/or tissue enzymes, resulting in autoimmune reaction in children with autism.
  PMID: 14611720 [PubMed - indexed for MEDLINE]

J Peripher Nerv Syst. 2004 Sep;9(3):165-7.  Related Articles, Links

Neuropathy and cognitive impairment following vaccination with the OspA protein of Borrelia burgdorferi. Latov N, Wu AT, Chin RL, Sander HW, Alaedini A, Brannagan TH 3rd.

Department of Neurology and Neurosciences, Weill Medical College of Cornell University, New York, NY, USA.

Abstract Neurological syndromes that follow vaccination or infection are often attributed to autoimmune mechanisms. We report six patients who developed neuropathy or cognitive impairment, within several days to 2 months, following vaccination with the OspA antigen of Borrelia burgdorferi. Two of the patients developed cognitive impairment, one chronic inflammatory demyelinating polyneuropathy (CIDP), one multifocal motor neuropathy, one both cognitive impairment and CIDP, and one cognitive impairment and sensory axonal neuropathy. The patients with cognitive impairment had T2 hyperintense white matter lesions on magnetic resonance imaging. The similarity between the neurological sequelae observed in the OspA-vaccinated patients and those with chronic Lyme disease suggests a possible role for immune mechanisms in some of the manifestations of chronic Lyme disease that are resistant to antibiotic treatment.

PMID: 15363064 [PubMed - in process]

November 02, 2004 06:00 AM US Eastern Timezone

La Jolla Institute for Allergy & Immunology Scientists Make Important Finding on Virus' Role in Autoimmune Diseases


SAN DIEGO--(BUSINESS WIRE)--Nov. 2, 2004--  Research Could Lead to Future Treatment Advances for Diabetes and Other Autoimmune Diseases      

Researchers at the La Jolla Institute for Allergy & Immunology have added a significant milestone to scientific understanding of the role viruses play in the development of autoimmune diseases, such as diabetes. Matthias von Herrath, M.D., and a team of scientists found that while viruses alone do not initiate autoimmune diseases, they can accelerate their development when paired with a genetic predisposition to autoimmune diseases.

This discovery, based on controlled laboratory studies of mice, represents the first demonstration in a living organism of the ability of viruses to increase the likelihood of the development of autoimmune diseases. The finding is an important advance and could help in the future development of therapies for the treatment or prevention of diabetes and other autoimmune illnesses.

The finding was published Monday in a scientific paper in the Journal of Clinical Investigation entitled, "A Viral Epitope that Mimics a Self Antigen Can Accelerate But Not Initiate Autoimmune Diabetes." In autoimmune diseases, the immune system, which normally wards off invading viruses and bacteria, instead mistakenly attacks normal body tissues, leading to illness. Dr. von Herrath's study dealt with the autoimmune form or type I diabetes, but the findings can also be applied to other autoimmune diseases. Examples of other autoimmune diseases include lupus or SLE, multiple sclerosis (MS), and rheumatoid arthritis.

Dr. von Herrath's research focused on a concept known as "molecular mimicry" or cross-reactivity. This occurs when the body's immune system recognizes not only part of a virus, but also a molecule in the body that looks very similar, and begins attacking cells that have that molecule assuming it is an actual virus. "We knew from evidence that cross-reactivity is common, but what we didn't know was whether that could actually accelerate the development of autoimmune disease in some individuals," said Dr. von Herrath, adding that it has long been theorized to play a role. "We found that it is unlikely that this cross-reactivity causes disease in someone who is not genetically predisposed to an autoimmune disease," he said. "However, if you superimpose cross-reactivity to a virus onto a genetic predisposition to an autoimmune disease, then it is much more likely that you'll develop the disease, and it happens faster."

Dr. von Herrath said the finding opens the door to further research to find associations between certain viruses and certain genetic predispositions to autoimmune diseases. He said this could shape large scale clinical studies of people with existing autoimmune diseases, to identify -- through their medical histories -- which viruses, when paired with which genetic predispositions, can cause certain autoimmune diseases to erupt.

Mitchell Kronenberg, Ph.D., LIAI President and Scientific Director, said the finding has major implications for future advancements in protecting people from autoimmune diseases. "By building on this research, we may one day be able to advise people genetically predisposed to multiple sclerosis, for instance, to avoid certain viruses or bacteria or to be vaccinated against them in order to prevent actual development of autoimmune disease," he said.

About LIAI

Founded in 1988, the La Jolla Institute for Allergy and Immunology is a non-profit medical research center dedicated to increasing knowledge and improving human health through studies of the immune system. Researchers at the institute carry out studies designed to understand and lead to the development of cures for cancer, allergy and asthma, infectious diseases, and autoimmune diseases such as diabetes, inflammatory bowel disease and arthritis. The institute's research staff includes over 100 Ph.Ds.


Immunol Cell Biol. 2005 Feb;83(1):9-17. 

Immune dysregulation and self-reactivity in schizophrenia: Do some cases of schizophrenia have an autoimmune basis?

Jones AL, Mowry BJ, Pender MP, Greer JM.

Neuroimmunology Research Centre, School of Medicine, The University of Queensland, Brisbane, Australia.

Summary Schizophrenia affects 1% of the world's population, but its cause remains obscure. Numerous theories have been proposed regarding the cause of schizophrenia, ranging from developmental or neurodegenerative processes or neurotransmitter abnormalities to infectious or autoimmune processes. In this review, findings suggestive of immune dysregulation and reactivity to self in patients with schizophrenia are examined with reference to criteria for defining whether or not a human disease is autoimmune in origin. Associations with other autoimmune diseases and particular MHC haplotypes, increased serum levels of autoantibodies, and in vivo and in vitro replication of some of the functional and ultrastructural abnormalities of schizophrenia by transfer of autoantibodies from the sera of patients with schizophrenia suggest that, in some patients at least, autoimmune mechanisms could play a role in the development of disease. Recent findings regarding specific autoimmune responses directed against neurotransmitter receptors in the brain in patients with schizophrenia will also be reviewed.

The following is an excerpt from an article written by Dr. Bernard Rimland, Director of the Autism Research Institute, Based in San Diego; Editor of the Autism Research Review International; Founder of the Autism Society of America, and Father of a 44-year-old Autistic Son.

First, do no harm. If the multibillion-dollar vaccine industry had heeded Hippocrates' ancient dictum and concentrated on making vaccines safe, the 300% to 500% nationwide increase in autism probably would not have occurred. Concern for vaccine safety might have prevented the simultaneous sharp rise in other chronic and debilitating diseases such as asthma, allergies, attention deficit/hyperactivity disorder, learning disabilities, arthritis and Crohn's disease.

The cause of the skyrocketing rates of these disorders, like the rise in autism, has mystified the experts. Many thoughtful and informed people believe that medical over exuberance has resulted in an unintended trade-off: Vaccination against acute diseases such as measles and rubella has increased susceptibility to chronic disorders such as autism, asthma, arthritis and ADHD.

Those marvelous pesticides, herbicides, gasoline additives and other miracles of modern chemistry have a downside. While we now know that toxic pollution of the environment is bad news, we are just beginning to learn that pumping toxins--viruses, bacteria, mercury, aluminum and formaldehyde, for example--into the body in the form of vaccinations for immediate gain may prove to be costly in the long term. Those who share my view do not oppose vaccines. What we oppose is over-vaccination and unsafe vaccines.

Most people are shocked to learn that in recent years, the number of vaccine doses a child receives before entering school has risen to 33. There are more than 200 other vaccines--expensive and profitable--under development. In 1965, parents began telling me that their children became autistic upon getting the DPT (diphtheria, pertussis, tetanus) shot--a triple vaccine. When another triple vaccine, MMR, (measles, mumps, rubella) was introduced in the 1980s, the alarming reports from parents and the prevalence figures for autism rose sharply.

In his testimony before the House Government Reform Committee, Paul Offit, the chief of infectious diseases at Children's Hospital of Philadelphia--who acknowledged at the hearing that he also is paid by the Merck Co. to educate doctors about vaccines--attacked the "notion" that giving three vaccines at once is unsafe: "The newborn has billions of immunologic cells that are capable of responding to millions of different microorganisms. By quickly making an immune response . . . babies keep those bacteria from . . . causing serious disease. Therefore, the combination of the three vaccines contained in the MMR or even the 10 vaccines given in the first 2 years of life, is literally a raindrop in the ocean of what infants successfully encounter in their environment every day."

That is an absurd argument. If every child has such a marvelously effective immune system, why should we vaccinate them at all? Especially, why should we use vaccines containing levels of mercury that vastly exceed the upper limit of safety? Even minute amounts of mercury are highly toxic to nerve and immune system tissue. Don't just tell us vaccines are safe. Where are the scientific data? There are none. It is no secret that the government's Vaccine Adverse Event Reporting System is not enforced and that doctors report only 1% to 10% of the adverse reactions they learn about.

Congress made a major mistake in enacting the National Vaccine Injury Compensation Act in the 1980s. It transferred liability for unsafe vaccines from the manufacturer to families through a surcharge on each vaccination.

This article makes a strong case for much more intense research on vaccines and safety. In reviewing other articles about vaccine and safety, the arguments saying vaccines were perfectly safe were always countered with statistical, factual data to the contrary. Very often, there were connections between the drug companies who manufacture vaccines and the people claiming the safety of vaccines.

While there is always room for debate over these statements, further research is imperative. To date, although the connections seem present, no one has proved that vaccines play a role in autism. However, no one has proved conclusively that they do not.


Without question, there are many causes of autism, and many subtypes of autism, only some of which may be expected to be largely caused by genetic abnormalities. Physiologic factors that may affect brain development, such as lipids, molecules involved in the working of the immune and nervous systems and that govern how cells communicate, how chemicals are handled by the body, how the immune system moves into action, chromosomes where defective genes are likely to be found, a missing piece of a chromosome, genetic changes, and specific genes are all being researched as to their possible connection to autism. Studies show the following in relation to autism and genetics:

an individual is 25 times more likely to have autism if sibling does 75% with autism have an affected identical twin there is clear genetic predisposition but no consistent chromosomal link what triggers those that are predisposed is unknown

Autoimmune Disorders

According to the authors of a U.S.-based study, the incidence of autoimmune disorders is increased in the mothers and other relatives of patients with autism. According to the study, autism was 8.8 times more likely in subjects whose mothers had autoimmune disorders, and 6.0 times more likely if first-degree relatives had autoimmune disorders. An increased number of autoimmune disorders suggests that in some families with autism, immune dysfunction could interact with various environmental factors to play a role in autism pathogenesis. Common autoimmune disorders in both [autistic and control] groups were type 1 diabetes, adult rheumatoid arthritis, hypothyroidism, and systemic lupus.


There has been speculation among parents and health professionals that the exposure of unborn and newborn infants to various metals or chemicals may trigger autism. There are research programs currently underway that are testing whether children's developmental problems can be linked to their exposures, while in the womb and as newborns, to pesticides, environmental tobacco smoke and lead; the impact of exposure to mercury and PCBs; how exposure to environmental toxins influences the neurological health and development of children; and other environmental factors that may be related to autism. In one report, a Brick Township, N.J., working class town with a well-known toxic landfill was found to have three times the normal autistic occurrence.


There are many theories as to the cause of autism but the truth is, as of now the current cause of autism is an unknown. It’s a complex biological disorder, and no two people with autism are the same. These differences lead scientists to believe that autism is the result of a mixture of causes. Vaccines, genetics, auto immune disorders and the environment are all suspect when is comes to what causes autism. There is various research currently being conducted in all these areas. There are numerous studies underway to try and determine the cause but to date no conclusion can be reached. More than likely, it will be a long time before these studies provide answers and even then the debate will continue. It is highly likely that there is no one cause but rather an accumulation of causes such as being genetically predisposed along with exposure to environmental toxins.


Subject: Molecular mimicry/virus abstracts

J Immunol. 2005 Jan 15;174(2):907-17.   Related Articles, Links    
Viral delivery of an epitope from Haemophilus influenzae induces central nervous system autoimmune disease by molecular mimicry.

Croxford JL, Anger HA, Miller SD.

Department of Microbiology-Immunology, and Interdepartmental Immunobiology
Center, Northwestern University Medical School, Chicago, IL 60611, USA.

Multiple sclerosis (MS) is an autoimmune CNS demyelinating disease in which infection may be an important initiating factor. Pathogen-induced cross-activation of autoimmune T cells may occur by molecular mimicry. Infection with wild-type Theiler's murine encephalomyelitis virus induces a late-onset, progressive T cell-mediated demyelinating disease, similar to MS. To determine the potential of virus-induced autoimmunity by molecular mimicry, a nonpathogenic neurotropic Theiler's murine encephalomyelitis virus variant was engineered to encode a mimic peptide from protease IV of Haemophilus influenzae (HI), sharing 6 of 13 aa with the dominant encephalitogenic proteolipid protein (PLP) epitope PLP(139-151). Infection of SJL mice with the HI mimic-expressing virus induced a rapid-onset, nonprogressive paralytic disease characterized by potent activation of self-reactive PLP(139-151)-specific CD4(+) Th1 responses. In contrast, mice immunized with the HI mimic-peptide in CFA did not develop disease, associated with the failure to induce activation of PLP(139-151)-specific CD4(+) Th1 cells. However, preinfection with the mimic-expressing virus before mimic-peptide immunization led to severe disease. Therefore, infection with a mimic-expressing virus directly initiates organ-specific T cell-mediated autoimmunity, suggesting that pathogen-delivered innate immune signals may play a crucial role in triggering differentiation of pathogenic self-reactive responses. These results have important implications for explaining the pathogenesis of MS and other autoimmune diseases.

PMID: 15634913 [PubMed - in process]   

Do Immune System Diseases Have an Environmental Cause?

Mercury. At California’s Scripps Research Institute, K. Michael Pollard says mice with a lupus gene will develop the disease when exposed to the level of mercury most of us carry in our bodies every day (0.04 micrograms). “It’s certainly a concern if you are someone with a family background of autoimmune disease,” Pollard says. “If you eat a lot of fish, you might want to be careful about it.” Similar experiments showed lupus-prone mice developed the disease after taking a very high dose of thimerosal, the mercury-based preservative in some vaccines. Pollard says no one has studied how thimerosal might affect children with a family history of autoimmune disease. But he believes the benefits of vaccines outweigh the risk.

“Acute Autoimmune Hemolytic Anemia Following DTP Vaccination:
Report of a Fatal Case and Review of the Literature” Clinical Pediatrics (06/01) Vol. 40, No. 6, P. 355; Downes, Katharine A.; Domen, Ronald E.; McCarron, Karen F.
This study reviews the case of an African-American female infant who experienced severe anemia and a drop in hemoglobin levels and was admitted to the hospital in an unresponsive condition at just four months of age. Admitted to the hospital between her fifth and sixth week, the infant exhibited unusual irritability and was tested for possible meningitis or sepsis, and then was empirically treated with a combination of ceftaxime and ampicillin and released in good health. At four months of age, the child was given her second doses of the oral polio virus, hepatitis B, and diphtheria, tetanus, and pertussis (DTP) vaccines, and within four days she exhibited lethargy, a low level fever, and lack of appetite. She was unresponsive when admitted to the hospital three days later, suffering from severe anemia and low hemoglobin levels. Tests for Haemophilus influenza, Streptococcus pneumoniae, and Neiseria meningitidis were negative or did not appear conclusively as cause or contributor to the current condition. The infant continued to experience severe hemolysis and died 41 hours after admission. Although the study could not prove it conclusively, by eliminating other causes of autoimmune hemolytic anemia (AIHA), the researchers suggest that, in this case, there is “a causal relationship to the second DTP vaccination.” A 1992 report from the Institute of Medicine concluded, however, that there is insufficient evidence of either the presence or absence of such a connection.

Vaccine ingredients could trigger autoimmune disease

6 August 2003 15:00 GMT
by Helen Dell

Mineral oils that are components of some vaccines induce the production of pathogenic autoantibodies and an inflammatory immune response when injected into mice, report US researchers. They suggest that these oils could be inducing autoimmunity in susceptible people.

The oils are used as adjuvants in vaccines - substances that enhance the immunogenicity of an antigen. It has been known for some time that some mineral oils can induce autoimmunity in the form of arthritis, indeed they are injected into mice to produce animal models for arthritis.

Now, Minoru Satoh, research associate professor at the Division of Rheumatology and Clinical Immunology at the University of Florida, and colleagues have examined at the oils' effect in another autoimmune disease - systemic lupus erythematosus (SLE).

SLE is a systemic autoimmune disease characterized by fever, weakness, arthritis, skin rashes, pleurisy and kidney dysfunction. Individuals produce autoantibodies to a wide array of tissue antigens, including DNA, histones, platelets, leucocytes, and many others.

Satoh's team injected mice with the most common oil adjuvants used in human and veterinary vaccines, incomplete Freund's adjuvant (IFA) and squalene, and tested to see whether SLE-specific antibodies were produced.

They found that up to a quarter of the mice produced autoantibodies that are SLE-specific. "The induction of autoantibodies was highly selective," they note. The ability of the oils to produce autoantibodies appears to correlate with the production of the inflammatory mediator molecules IL-12, IL-6 and TNF-alpha.

"I think this is a very significant finding because there is a possibility that vaccination in animal or human can induce lupus autoantibodies in susceptible individuals," said Satoh.

His team are now testing the effects of medicinal mineral oil and other adjuvant components. "Hopefully, we can find some safe [mineral oil] that can be used as adjuvant but doesn't induce lupus autoantibodies," he said.

The researchers are also beginning to look for genetic factors that might influence susceptibility to SLE autoantibody production. They have tested
25 common laboratory strains of mice, each of which has a slightly different, well-defined genotype. However, mice from all the strains produced the SLE autoantibodies after injection with mineral oils, making it difficult to separate out the genes that might underlie susceptibility.

Thomas Aune, Associate Professor of Medicine at Vanderbilt University in Nashville, Tennessee, has been looking at gene expression patterns in people with autoimmune disease to see how they differ from patterns in people without disease. He is cautious about the new results.

Environmental insults that are proposed to cause autoimmunity have waxed and waned in popularity over the years, he says, but none have really stood the test of time.

Subject: Maternal antibodies may contribute to autism

NEW YORK (Reuters Health) - Along with genetic, metabolic and environmental factors, a team of researchers at Johns Hopkins University in Baltimore suggest that autism may also be caused or triggered by maternal antibodies that cross over through the placenta and are directed against the brain tissues of the fetus, adversely affecting brain development.

Dr. Harvey S. Singer and colleagues note that children with autism have antibodies in the blood that react against brain tissue. Antibodies are an important part of the immune system in which proteins are produced and mount a defense in response to the presence of a foreign body, such as an invading virus.

Most studies into the origin of autism have focused on autoantibodies as a possible explanation. Autoantibodies are antibodies the body makes that react against the body's own tissues by mistake; this mechanism is involved in allergic reactions and autoimmune diseases.However, another possible explanation involves the transfer of reactive antibodies from the mother through the placenta to the fetus. To investigate the latter, the team measured the antibody-brain reaction in blood samples from 100 mothers with and 100 mothers without a child diagnosed with autism. Mothers of children with autism had a stronger reactivity or more areas of reactivity between antibodies and brain proteins compared with mothers without an autistic child. The presence of maternal antibodies also correlated with having a child with developmental regression, a primary feature of autism. "Our research suggests that the mother's immune system may be yet another factor or trigger in those already predisposed" to autism, Singer commented in a university release.

"The mere fact that a pregnant woman has antibodies against the fetal brain doesn't mean she will have an autistic child," Singer cautioned. "Autism is a complex condition and one that is likely caused by the interplay of immune, genetic and environmental factors."The researchers are now studying the effect of maternal antibodies in pregnant mice. Preliminary results show that the offspring of mice injected with neural antibodies exhibit developmental and social
behaviors suggestive of autism.

SOURCE: Journal of Neuroimmunology, February 2008.


Possible Immunological Disorders in Autism: Concomitant Autoimmunity
and Immune Tolerance

Maha I. Sh. Kawashti, Omnia R. Amin, Nadia G. Rowehy
Egypt J Immunol. 2006;13(1):99- 104.


Autism is a pervasive developmental disorder that affect children early in their life. Immunological disorders is one of several contributing factors that have been suggested to cause autism. Thirty autistic children aged 3-6 years and thirty non-autistic psychologically- free siblings were studied. Circulating IgA and IgG autoantibodies to casein and gluten dietary proteins were detected by enzyme-immunoassays (EIA). Circulating IgG antibodies to measles, mumps and rubella vaccine (M.M.R) and cytomeglovirus were investigated by EIA. Results revealed high seropositivity for autoantibodies to casein and gluten: 83.3% and 50% respectively in autistic children as compared to 10% and 6.7% positivity in the control group. Surprisingly, circulating anti-measles, anti-mumps and
anti-rubella IgG were positive in only 50%, 73.3% and 53.3% respectively as compared to 100% positivity in the control group. Anti-CMV IgG was positive in 43.3% of the autistic children as compared to 7% in the control group. It is concluded that, autoimmune response to dietary proteins and deficient immune response to measles, mumps and rubella vaccine antigens might be associated with autism, as a leading cause or a resulting event. Further research is
needed to confirm these findings.

PMID: 17974154


"Autoantibodies" May Be Created In Response To Bacterial DNA

Autoimmune diseases have long been regarded as illnesses in which the immune system creates autoantibodies to attack the body itself. But today, researchers at the California non-profit Autoimmunity Research Foundation (ARF) explain that the antibodies observed in autoimmune disease actually result from alteration of human genes and gene products by hidden bacteria.

Not long ago, scientists believed they had located all bacteria capable of causing human disease, But DNA discoveries in the last decade have led the NIH Human Microbiome Project to now estimate that as many as 90% of cells in the body are bacterial in origin. Many of these bacteria, which have yet to be named and characterized, have been implicated in the progression of autoimmune disease.

In a paper published in Autoimmunity Reviews, the ARF team, under the guidance of Professor Trevor Marshall of Murdoch University, Western Australia, has explained how Homo sapiens must now be viewed as a superorganism in which a plethora of bacterial genomes a metagenome work in concert with our own. Marshall and team contend that the human genome can no longer be studied in isolation.

"When analyzing a genetic pathway, we must study how bacterial and human genes interact, in order to fully understand any process related to the human superorganism," states Marshall. "Especially since some of these pathways contribute to the pathogenesis of autoimmune disease."

For example, the team notes that the single gene ACE has an impact on myocardial infarction, renal tubular dysgenesis, Alzheimer's, the progression of SARS, diabetes mellitus, and sarcoidosis, yet recently ACE has been shown to be affected by the common species Lactobacillus and Bifidobacteria. Found in yogurt, these species are often considered to be innocuous or "friendly."

"No one would argue that these species aren't present in the human body, yet there has been inadequate study of how these 'friendly' species affect disease," states Amy Proal, the paper's lead author.

"What we thought were autoantibodies generated against the body itself can now be understood as antibodies directed against the hidden bacteria," states Marshall. "In autoimmune disease, the immune system is not attacking itself. It is protecting the body from pathogens."

To validate their lab discoveries, Marshall's team has been conducting an observational clinical trial of more than 500 autoimmune patients and reported at the recent 6th International Congress on Autoimmunity that antibacterial therapies targeted at these hidden microbes are capable of reversing autoimmune disease processes.

Source: Autoimmunity Research, Inc

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