Restricted Heterogeneity and T cell Dependence of Human Thyroid Autoantibody Immunoglobulin G Subclasses*

Abstract

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 IgGl and/or IgG4 subclasses. The contribution of each subclass to an individual autoantibody titer varied from 100% IgGl to 100% IgG4. Sixteen of the 25 sera had detectable hTg-Ab, and the majority also were restricted to IgGl 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, IgGl, but not IgG 2, 3, or 4, had T cell dependence, as evidenced by enhancement and inhibition of IgGl 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 IgGl subclass secretion. These data indicate 1) restricted heterogeneity of human thyroid autoantibodies, principally to IgGl and IgG4; 2) T cell dependence of only IgGl secretion in vitro; and 3) a T cell defect in patients with autoimmunethyroid disease. The possibility of IgG4 thyroid autoantibodies being under less stringentT cell regulatory control questions the likely importance of thyroidspecific suppressorTcell dysfunction in the etiology of autoimmune thyroid disease.