Immunologic aspects of Graves' and Hashimoto's diseases

It is hypothesized that Graves' hyperthyroidism, exophthalmos, and Hashimoto's thyroiditis (as well as other closely related organ-specific autoimmune disorders) may each be attributed to separate, albeit very closely related, inherited isolated defects in immunoregulation (possibly specific defects in suppressor T lymphocyte function). The gene responsible for each of these disorders may lie in close linkage disequilibrium with HLA-Dw3 on chromosome 6. Each of the defects in immunoregulation, however, would permit a specific randomly mutating self-reactive “forbidden” clone of “helper” T lymphocytes to survive (if it chanced to appear), interact with its complementary antigen, and induce a cell-mediated immune response. This would not require any alteration of the antigen, only the mere availability of the specific antigen. The clone of self-reactive T lymphocytes, so arising and escaping immunoregulation, would presumably then expand upon interaction with its antigen, and consequently direct and cooperate with appropriate groups of (already present) B lymphocytes, which in turn would produce specific immunoglobulins that appear necessary for the full expression of these disorders. Adjunctive roles for immune complexes, nonspecific cells (macrophages, “killer” cells), and chemical mediators are undoubtedly important. The role of stress in the induction of hyperthyroidism may be by means of its effect in further reducing immunosuppression in those persons with only a partial isolated defect. On the other hand, remissions may be brought about by restoring immunoregulation to its previous state. Those persons having an isolated complete defect in immunoregulation would not be expected to achieve remissions, except by destruction of thyroid parenchyma.