Studies on Autoimmune Mechanisms of Thyroglobulin Autoantibody in Autoimmune Thyroid Disease

In order to clarify the autoimmune mechanisms of anti-Tg antibody (anti-TgAb) in autoimmune thyroid disease (AITD), a series of examinations were conducted in patients with Graves' disease (n=59), Hashimoto's thyroiditis (n=63) and healthy controls (n=38). Our findings can be summarized as follows: 1) The distribution of anti-TgAb was measured by IgG subclass ELISA. IgG1 and/or IgG4 antibodies formed the major anti-Tg response, but in some patients, IgG2 anti-Tg tend to be the predominant response. We used ELISA to determine an IgG1 anti-Tg bound to Tg that had already interacted with IgG2 Tg-antibody (and vice versa). The results substantiated the view that TgAb of a different IgG subclass interacts with different epitopes on Tg. 2) Human antiidiotypic (anti-Id) antibodies to anti-Tg antibody occur spontaneously in the AITD. These anti-Id antibodies can be divided into two categories based on properties of their binding sites. One type acts like a 'internal image' of Tg antigen which shown Ab2β activity. Another type has Ab2α activity that recognizes Id determinants in the framework region common among anti-Tg antibody. 3) We also examined the competitive binding assay between TgAb and TgAb F(ab')2 fragments, and demonstrated differences in the TgAb repertoires between patients. 4) Soluble IL-2 receptor (IL-2R) of patients significantly increased as compared with normal subjects and IL-2R values in GD were higher than those in HT (p<0.001). Therefore, IL-2R is regarded as a useful marker for disease activity.