Igg Subclass Distribution of Anti-Tg Antibodies Among Thyroid Disease Patients and Their Relatives and in High and Low Responder Mouse Strains

Abstract

A large body of clinical and experimental evidence points to a genetic predisposition toward the development of autoimmune thyroid disease. During the past several years, work in our laboratory1 as well as by 2 others has resulted in significant progress in sorting out the several genetic factors that influence thyroid autoimmunity in human populations. In these investigations, we have derived considerable benefit from our earlier analyses of the genetic determinants of autoimmune thyroiditis in 3 the Obese strain (OS) chicken.3 This strain of birds develops a spontaneous form of thyroiditis that closely resembles human Hashimoto’s disease. It is marked by extensive mononuclear infiltration of the thyroid gland and production of thyroid-specific autoantibodies, especially to thyroglobulin (Tg). In our studies of the OS chicken, the key finding was that the occurrence of disease is not the result of any single gene, but rather a conglomeration of several unrelated genetic lesions. 4,5 We found no evidence for “disease susceptibility” genes as such. Rather, our findings suggested that genes widely distributed among chickens derived from the original Cornell colony have a number of consequences that, in the aggregate, favor the spontaneous development of autoimmune thyroid disease. We recognize that this view differs substantially from that of many other investigators, who suggest that etiology of autoimmune disease is based on an abnormal gene in the major histocompatibility complex (MHC).6