TF and Autistic Children 2

Autism, Autoimmunity and Immunotherapy: a Commentary by Vijendra K. Singh, Ph.D.

Department of Biology & Biotechnology Center, Utah State University, Logan

Scientific Board Member, Autism Autoimmunity Project

Autoimmune Etiology in Autism

A disease is commonly referred to as "autoimmune" when the etiology and pathogenesis is not well known or established. Autoimmunity is an abnormal immune reaction in which the immune system becomes primed to react against body organs, and the end result is autoimmune disease. Several factors contribute to the pathogenic mechanism of autoimmune diseases. These illnesses are commonly believed to be triggered by infectious agents; further, they are generally linked to genes that control immune responses. They cause immune abnormalities of T lymphocytes (one type of white blood cell); they induce the production of autoantibodies; they involve hormonal factors; and they generally show a gender preference. This is also the case with autism: several autoimmune factors have been identified in patients with autism, suggesting the pathogenetic role of autoimmunity in autism. While some of the key features are listed below, I will focus more on the current research relating to three topics: viral studies; autoimmune testing; and autoimmune therapy. Some generalities regarding the genetics and immunology of autism are below:

_ Autism displays increased frequency of genetic factors for immune responses, e.g., HLA, C4B null allele, extended haplotypes, etc.

_ Autism involves a gender factor, i.e., it affects males about four times more than females.

_ Autism often occurs in conjunction with a family history of autoimmune diseases, e.g., multiple sclerosis, rheumatoid arthritis, etc.

_ Autism also involves hormonal factors, e.g., secretin, beta-endorphin, etc.

_ Autism shows an association with infectious agents, in particular viruses.

_ Autistic patients have immune abnormalities, especially those that characterize an autoimmune reaction in a disease.

_ Autistic patients respond well to immune therapies.

Viruses have been linked to autism, but this relationship is far from fully explored. Certain viral infections can easily be acquired during fetal life, infancy or early childhood. They can enter the brain through the nasopharyngeal membranes or induce an autoimmune response against the brain, thereby altering the development of brain function. Since autism is an early-onset disorder, usually diagnosed before the age of 30 months, it was suggested that viruses might serve as teratogens (agents that cause developmental malfunctions) contributing to autism.

Recent advances have clearly shown that autoimmunity plays a key role in the pathogenesis of autism. Since the brain is the affected organ in autism, the autoimmune response will be directed against this organ. This response is commonly identified by certain autoimmune factors which I have identified in autistic children. The list includes brain-specific autoantibodies, viral antibodies, cytokine profile or immune activation markers, as well as antinuclear antibodies. Collectively, they are essential for identifying a brain-specific autoimmune response, which can afterward be treated with immune therapy. By performing blood tests we can determine if a patient shows autoimmunity to brain tissues, if he or she is a candidate for experimental immune therapy, and if the response to therapy is effective. Therefore, this type of immune evaluation is very important in helping children with autism

Recent Congressional Testimony on Autism
by Vijendra K. Singh, Ph.D. April 6, 2000

Today, I will be speaking about the autoimmunity aspect of vaccines in autism, a medical condition that has been largely ignored by the medical community and federal government for a very long time and yet the incidence of autism is increasing at an alarming rate.

An estimated one-half of a million Americans, mainly children, and millions more worldwide are known to suffer from autism, a heart-rending disorder that severely impairs higher brain functions: social interaction, communication, language, imagination and cognition. The disorder is a life-long mental disability with devastating consequences for both the patient and his/her family. Thus the financial burden is huge for the families who care for children with autism.

Autism is an idiopathic brain disorder, which simply means that the etiology of the disorder is not known. And there is no single, clear-cut cause for autism. Causally speaking, I tend to think that autism is a complex disorder, in which autoimmunity to brain plays a key role.

Today, in spite of virtually no funding available, autoimmunity is the most extensively investigated topic of research in autism. This is by and large due to the fact that autoimmunity is the prime target of therapy that has proven to be quite effective in ameliorating autistic characteristics. Thus the autoimmunity research, unlike the genetic research, has already significantly improved the health and welfare of individuals with autistic disorder.

I have recently coined a term "Autoimmune Autism (AA)" to refer to a subset of autism that has autoimmune etiology. Moreover, there are scientific reasons to think that this subset may indeed be a result of vaccine injuries to children who display autistic regression.

Autoimmunity is an abnormal reaction immune reaction, in which the immune system becomes primed to react against body organs. It's a mosaic of highly complicated interactions and networking between cells and molecules of the immune system.

The body makes autoantibodies against itself, resulting in damage to tissues and organs. The "autoimmune" response is what happens in autoimmune diseases such as lupus, and my research showed that a similar response my account for the brain abnormalities found in people with autism.

Autoimmune diseases are identified and characterized by many factors. The hallmark is the "organ-specific autoantibodies" that have also been identified in people with autistic disorder. To that end, I have recently summarized laboratory data of approximately 400 cases (autistic and controls) and found that up to 80% of autistic children have autoantibodies to specific brain structures, in particular a brain protein known as myelin basic protein (MBP) of the myelin sheath, a fatty coating that insulates nerve fibers and absolutely essential for higher brain functions.

These autoantibodies are present quite frequently (65-85%) in autistic children, but only rarely (0-5%) in normal children and other disease controls. Accordingly, I postulated that autism involves a specific autoimmune response to MBP -- an immune assault that impairs myelin development in the developing brain, thereby modifying the nerve cell functions of the brain. Ultimately, by way of impaired wiring diagram in the brain, this results into autism.

Autoimmunity is commonly triggered by environmental exposures such as viral infections. Virus serology (or virus antibodies) is an excellent tool for studying virus infections in disease states. However, until recently, such studies had not been performed for autism. Because of my ongoing research, I became interested in examining a virus link with autoimmunity in autism. I recently raised two specific questions:

(1) Do autistic children have a hyperimmune response (or increase of antibodies) for a specific virus?

(2) Is there a relationship between virus antibodies and brain autoantibodies in autism? I conducted a carefully designed study to address these two questions. Succinctly, I made two very important observations: first, there was indeed a hyperimmune response to a virus and it was specifically for the measles virus (MV), but not for the other viruses tested [human herpesvirus-6 (HHV-6), rubella virus (RV), and cytomegalovirus (CMV)]; and secondly, there was an association between measles virus antibodies and MBP autoantibodies (i.e., the higher the measles virus antibody level the greater the chance of brain autoantibody).

Few months earlier in the same year (February, 1998), I had already found that many autistic children had antibodies to a specific protein of the measles-mumps-rubella (MMR) vaccine (MMR vaccine preparation). These viral antibodies were also related to positive titers of brain MBP autoantibodies.

This was most probably the first laboratory-based evidence to link measles virus and/or MMR vaccine to autoimmunity in children with autism. Collectively, these observations led me to speculate that autism may be caused by a measles- or MMR vaccine-induced autoimmune response. Unfortunately, due to lack of funding, I have not been able to extend this research and the progress has been hampered.

As I made scientific presentation of my initial findings, a vaccine-autism connection became even more apparent. I compiled a nonscientific, anecdotal survey of vaccine-injured children with "autistic regression" or autistic disorder, as reported by families. Surprisingly, up to 93% of the reported cases had autistic symptoms shortly after vaccinations (52% post-MMR, 33% post-DPT, and 8% post-MMR and/or post-DPT).

The remaining 7% of the reported cases were not linked to any vaccination at all. Indeed, if these numbers are reproducible, the data will lead to inescapable conclusion that these vaccines can potentially cause autoimmunity in autism. Quite candidly, this will not be first time that a vaccine has been linked to a disease or disorder. There is quite a bit of literature linking vaccines to autoimmune diseases.

Furthermore, an epidemiological study just published in JAMA (March 8, 2000) described "extraimmunization" amongst American children and considered it to be a contributing factor for the adverse effects of the vaccines. And I think the vaccines and autism connection is no exception to these adverse effects.

In summary, the rapidly accumulating evidence strongly implicates autoimmunity in autism, which in many may result from a vaccine injury. There is a possibility of an atypical measles infection in autism, but the evidence also suggests a MMR vaccine infection.

Without any reservation, I would strongly recommend that this Congressional Committee reviews all the information in bipartisanship, and explore the possibility that drug companies never properly evaluated the safety of vaccines in the first place. If this indeed were true then it becomes imperative that we as a society must pay an immediate attention to this problem; otherwise, an epidemic of autism is a real good possibility.

There should be no mistaking about it because autism is on a sharp rise and vaccinations, especially the extraimmunization, could potentially explain this rise. The onset of autism (or autistic regression) post-immunization should no longer be regarded as merely a coincidence with the timing of the vaccinations, as our federal health officials continue to do.

We must find new ways to curve adverse effects of vaccines, including autism. Considering a population of 500,000 cases of autism in the United States, the autoimmunity research, but not the genetic research, has already had a great impact on the health and welfare of autistic people. Since brain autoimmunity is found in up to 85% of cases, it can potentially help an estimated 425,000 Americans.

Indeed, many of them are already reaping the benefits of the experimental autoimmune therapy. Thus there is an urgent need to promote autoimmunity research in autism. This recommendation is in contrast to the opinions held by the directors of the federal agencies and major private foundations (Cure Autism Now and National Alliance for Autism Research) who are erroneously committed themselves to fund genetic research only.

Finally, I urge the Government Reform Committee to provide leadership for new solutions to the existing problems surrounding autism research, and request the Committee Members to be visionary and offer new hope to the people with autism -- The essence of life is to care.