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We report an experimental study designed to test the following hypothesis derived from clinical observations: There is an elevated frequency in left-handed individuals and in their families of immune disease, migraine, and developmental learning disorders. In two separate investigations the frequency ofthese conditions was compared -in strongly left-handed subjects and -in strongly right-handed controls. In each of the investigations we found markedly higher frequencies of immune disease in the lefthanders than in the rightphanders. The rate of learning disabilities was also much higher in the left-handers than in the right-handers in both investigations. In a second study the frequency of lefthandedness was compared in patients with migraine or immune disease and in general population control subjects free of these disorders. There was' a higher frequency of left-handedness in patients with migraine and myasthenia gravis than in controls. We present a brief outline of a hypothesis that may account for an increased frequency of immune disease in left-handers and in their families.Cerebral dominance-i. e., greater proficiency ofeach cerebral hemisphere in acquisition and performance of certain specific functions-has been recognized as a biological characteristic of humans' for over 100 years. In most people there is dominance ofthe left hemisphere for language and ofthe right side for certain spatial functions. The older literature dealt predominantly with humans, with major stress on the laterality of lesions producing certain cognitive deficits. Since World War H' there have been many studies that demonstrate dominance in normals.By contrast, few studies on laterality deal with the kinds of data that are often found in studies ofother biological traits, such as eye color. Examples of such data include the anatomical structures involved, biochemical and' immunological properties, genetics, ontogeny, evolution, and comparative features in other species. In older publications one finds a few discussions ofassociations ofhandedness, such as asymmetries in fingerprints (1). More recent studies deal with anatomical asymmetries in the human brain, especially in language areas (2-6), asymmetries of function and structure in other species (7-11), the genetics of handedness (10, 12, 13), and the relationship of sinistrality to learning disabilities and to artistic, athletic, and other -talents (12,14). Anatomical maldevelopment has been demonstrated in the left side of the cortex (15) and in the thalamus (16) of a left-handed childhood dyslexic. These studies reflect growing interest in the' biological associations of dominance.Since the autumn of 1980, one of us (N.G.) has been impressed by observations on both patients and normals with an apparently elevated frequency ofcertain disorders in left-handers and in their families, including immune disorders (e.g., ulcerative colitis, celiac disease, and Hashimoto's thyroiditis) and migraine. Developmental learning disorders (e. g., dyslexia and stuttering) were als...

Antigens of pathogenic microbes that mimic autoantigens are thought to be responsible for the activation of autoreactive T cells. Viral infections have been associated with the development of the neuroendocrine autoimmune diseases type 1 diabetes and stiffman syndrome, but the mechanism is unknown. These diseases share glutamic acid decarboxylase (GAD65) as a major autoantigen. We screened synthetic peptide libraries dedicated to bind to HLA-DR3, which predisposes to both diseases, using clonal CD4 ؉ T cells reactive to GAD65 isolated from a prediabetic stiff-man syndrome patient. Here we show that these GAD65-specific T cells crossreact with a peptide of the human cytomegalovirus (hCMV) major DNA-binding protein. This peptide was identified after database searching with a recognition pattern that had been deduced from the library studies. Furthermore, we showed that hCMV-derived epitope can be naturally processed by dendritic cells and recognized by GAD65 reactive T cells. Thus, hCMV may be involved in the loss of T cell tolerance to autoantigen GAD65 by a mechanism of molecular mimicry leading to autoimmunity.

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We have examined the muscle biopsies of 50 patients who had postviral fatigue syndrome (PFS) for from 1 to 17 years. We found mild to severe atrophy of type II fibres in 39 biopsies, with a mild to moderate excess of lipid. On ultrastructural examination, 35 of these specimens showed branching and fusion of mitochondrial cristae. Mitochondrial degeneration was obvious in 40 of the biopsies with swelling, vacuolation, myelin figures and secondary lysosomes. These abnormalities were in obvious contrast to control biopsies, where even mild changes were rarely detected. The findings described here provide the first evidence that PFS may be due to a mitochondrial disorder precipitated by a virus infection.

Objective-To study the dynamic function of hypothalamic 5-hydroxytryptamine receptors in patients with postviral fatigue syndrome.Design-Prospective comparison of patients with postviral fatigue syndrome with two control groups.