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.
AuthorsD D Adams, Y J Adams, J G Knight, J McCall, P White, R Parkinson, R Horrocks, E van Loghem
JournalLife sciences (Life Sci) 1983 Jan 3-10 Vol. 32 Issue 1-2 Pg. 3-13 ISSN: 0024-3205 [Print] ENGLAND
PMID6687484 (Publication Type: Journal Article)
Chemical References
  • HLA Antigens
  • Immunoglobulins
  • Animals
  • Female
  • Genes
  • Graves Disease (genetics, immunology)
  • HLA Antigens (genetics)
  • Humans
  • Immunoglobulins (analysis)
  • Male
  • Mice
  • Mice, Inbred NZB

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