Restricted heterogeneity and T cell dependence of human thyroid autoantibody immunoglobulin G subclasses

Twenty-five sera from patients with autoimmune thyroiditis, positive for thyroglobulin (hTg) and/or thyroid microsomal autoantibodies (M-Ab), were assessed by specific micro-ELISA to determine thyroid autoantibody immunoglobulin G (IgG) subclass distribution. Of the 25 sera, 22 were positive for M-Ab. All but 1 sample had restricted heterogeneity confined to IgG1 and/or IgG4 subclasses. The contribution of each subclass to an individual autoantibody titer varied from 100% IgG1 to 100% IgG4. Sixteen of the 25 sera had detectable hTg-Ab, and the majority also were restricted to IgG1 and IgG4, with similar distributions occurring among subclasses. In all, only 5 sera had hTg/M-Ab in IgG subclasses 2 and/or 3. T cell control of pokeweed mitogen-stimulated IgG subclass secretion was analyzed using increasing numbers of T cells in ratios of T to non-T from 0:1 to 10:1. In normal subjects, IgG1, but not IgG 2, 3, or 4, had T cell dependence, as evidenced by enhancement and inhibition of IgG1 secretion as the number of T cells increased. T cell suppressor dysfunction was apparent in patients with autoimmune thyroiditis, as demonstrated by the reduced ability of patient T cells (n = 6), compared with normal T cells (n = 6), to suppress total IgG1 subclass secretion. These data indicate 1) restricted heterogeneity of human thyroid autoantibodies, principally to IgG1 and IgG4; 2) T cell dependence of only IgG1 secretion in vitro; and 3) a T cell defect in patients with autoimmune thyroid disease. The possibility of IgG4 thyroid autoantibodies being under less stringent T cell regulatory control questions the likely importance of thyroid-specific suppressor T cell dysfunction in the etiology of autoimmune thyroid disease.