Resolving a chaotic paradox: autism as a disease of the developing immune system
This lecture provides an overview of the "new" autism as a primary disturbance of the immune system and critically, misprogramming of the infant immune system leading to autoimmunity and immunological intolerance. Central to immune system perturbation is an environmental exposure(s) that result in lymphopenia (reduction in the number of blood lymphocytes). This leads to homeostatic T cell expansion (HTE) in the peripheral lymphoid tissues such as the intestine, in an effort to restore the naive T cell pool. The consequences of HTE include lymphoid hyperplasia, bacterial translocation from the gut into the body, impaired regulatory T cells (Treg) function, colitis, and proinflammatory immune responses directed against intestinally-derived antigens (food and bacteria) and self i.e., autoimmunity. It is proposed that immune responses against intestinally-derived antigens cross-react with host antigens present in the brain, leading to neurological injury. Human and experimental models of immune encephalopathy and experience with HIV/AIDS are used to support this concept in the setting of autism.
Andrew Wakefield, MB, BS, FRCS, FRCPath is an academic gastroenterologist. He graduated in Medicine from St. Mary's Hospital (part of the University of London) in 1981, pursuing a career in gastrointestinal surgery with a particular interest in inflammatory bowel disease. He qualified as Fellow of the Royal College of Surgeons in 1985, and in 1996 was awarded a Wellcome Trust Traveling Fellowship to study small-intestine transplantation in Toronto, Canada. Discoveries made during his work in Canada led him on return to the UK to pursue the study of inflammatory bowel diseases such as Crohn's disease and ulcerative colitis. In 1998, he and his colleagues at the Royal Free Hospital in London reported a novel inflammatory bowel disease in children with developmental disorders such as autism; the condition later became known as autistic enterocolitis. Dr. Wakefield resisted pressure to stop his research on the possible links between childhood immunizations, intestinal inflammation and autism, leaving the Royal Free School of Medicine in 2001. He is involved in many scientific research collaborations in the U.S and abroad, investigations centering on the immunologic, metabolic, and pathologic changes occurring in inflammatory bowel diseases such as autistic enterocolitis, links between intestinal disease and neurologic injury in children, and the possible relationship of these conditions to environmental causes, such as childhood vaccines. During the course of his work on childhood developmental disorders, Dr. Wakefield was increasingly convinced of the need for a research-oriented, integrated bio-medical and educational approach to these disorders, in order to translate clinical benefits for affected children into measurable developmental progress; this is the driving aim of Thoughtful House. As of the beginning of 2007, Dr. Wakefield has published one hundred thirty-four original scientific articles, book chapters, and invited scientific commentaries. He was awarded the Fellowship of the Royal College of Pathologists in 2001; he is medical advisor to the United Kingdom charity Visceral, and sits on the board of the U.S. charity Medical Interventions for Autism.