Immunoregulation abnormalities in familial Addison's disease.

Abstract

Three brothers, two with Addison's disease and a monozygous twin discordant for adrenal insufficiency, presented an unique opportunity to evaluate the endocrine and immunological abnormalities associated with this disorder. None of the brothers had clinical evidence of other autoimmune disease. However, each of the twins had elevated titers of antihydroglobulin and antiparietal cell antibodies, and both Addisonian siblings had cytoplasmic islet cell antibodies. We evaluated the ability of nonspecific Concanavalin A-activated suppressor cells from all three siblings to inhibit immunoglobulin biosynthesis by pokeweed mitogen-stimulated B cells, cell proliferation by phytohemagglutinin-stimulated T cells, and the proliferative response of an allogenic mixed lymphocyte culture. In comparison to normal controls, suppressor cells from the Addisonian siblings were less efficient in inhibiting both B and T cell activities. The nonAddisoninan twin had a lesser degree of impaired suppressor cell function to the B and T cell targets. Suppressor cell activity, as measured by the ability to inhibit proliferation within the mixed lymphocyte culture, was normal in all three siblings. The relationship of suppressor cell dysfunction, genetic predisposition, and the expression of the autoimmune state are discussed.