Neutralization of long-acting thyroid stimulator by antibodies to euthyroid human serum.
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Biomedical subjects
D D Adams
Publications and source records attributed to D D Adams.
On the nature of the genes influencing the prevalence of Graves' disease.
Burnet's theory that Graves' and other autoimmune diseases are caused by forbidden clones of immunocytes, reactive against host antigens and emerging in post-natal life due to somatic events (somatic mutations of V genes and inter-clonal deletions), remains the most comprehensive and likely concept of the pathogenesis. The MHC antigens, B8 and D/DR3, have a predisposing influence of X 2.5 and X 3.7 respectively, whilst male sex has a protective influence, divided by 6. Family studies testing for associated inheritance of Graves' disease and immunoglobulin allotypes (Gm and Km), by observation of the segregation of known heterozygous allotypes and also by Penrose's sibling pair method, have failed to show involvement of immunoglobulin genes. The H gene theory, prompted by studies on the inheritance of autoimmune diseases in the New Zealand mice, postulates that germline genes influencing the prevalence of Graves' and other autoimmune diseases code for major and minor histocompatibility or other alloantigens. By deleting complementary clones, alloantigens alter the immune response repertoire of each individual and this could alter the chance of emergence of a forbidden clone by the somatic mutations and the inter-clonal deletions envisaged by Burnet and Jerne. The H gene theory is superior to the linkage disequilibrium theory in that it accounts for all the known genetic features of Graves' disease, including the female sex preponderance, which is ascribed to the effect of clonal deletions imposed by the H-Y antigen.
Animals↗
An informative case of Graves' disease with implications for schizophrenia.
The aetiology of schizophrenia and the other psychoses is not yet established. The Knight model, based on genetic and other evidence, proposes that schizophrenia is an autoimmune disease, caused by the development of forbidden clones of B lymphocytes that secrete autoantibodies that accidentally stimulate cell surface receptors on certain neurons, affecting the limbic system of the brain. An unusual defect in a Maori man with Graves' disease rendered him unresponsive to the usually effective antithyroid drugs, prompting his being treated with prednisone, a non-specific immunosuppressant agent. This was highly successful, reducing the blood level of the causative thyroid-stimulating autoantibodies with reduction of thyroid hormone levels and thyroid gland size. Unfortunately, high dosage prednisone can be used for only a month, because of steroid toxicity. A research pathway to effective therapy of receptor-mediated autoimmune diseases, which probably include the psychoses, is now apparent. It involves finding the autoantibodies, then cloning of their antigenic targets, as has been done for Graves' disease. This will provide knowledge of the peptide sequences necessary for constructing therapeutic agents for selectively destroying the pathogenic forbidden clones. Meanwhile, usage of short-term therapy with prednisone could be helpful in the management of schizophrenia and should be explored.
Antithyroid Agents↗