Evidence for a restricted idiotypic and epitopic specificity of anti-thyroglobulin autoantibodies in patients with...

Anti-thyroglobulin (TG) autoantibodies from patients with autoimmune thyroiditis express a cross-reactive alpha idiotype (Id) termed T44 which is not expressed by IgG from normal individuals. The present study demonstrates that the expression of the T44 Id is strongly associated with the recognition by anti-TG autoantibodies of a specific epitopic cluster on human TG. The epitopic reactivity of anti-TG autoantibodies was determined using a competitive inhibition assay with a panel of 15 monoclonal antibodies that define six antigenic clusters on TG. All T44+ autoantibodies from patients recognized cluster II, whereas no anti-TG IgG from healthy individuals reacted with this region. Affinity columns of Sepharose-bound intravenous therapeutic immunoglobulins which contain anti-T44 activity, retained both T44 Id-expressing antibodies and a subset of region II-specific anti-TG autoantibodies from patients with Hashimoto's disease. Restricted idiotypic and epitopic specificity may demarcate disease-associated from natural anti-TG autoantibodies, suggesting that qualitative rather than quantitative criteria should be used to identify pathological autoantibodies.