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THE PUTATIVE ANTI‐THYROTROPIN RECEPTOR ANTIBODIES OF GRAVES' DISEASE:I. Gm ALLOTYPES *

The hyperthyroidism of Graves' disease is thought to be related to antithyrotropin receptor (TSH‐R) antibodies. In order to study the degree of immunogenetic homogeneity of these antibodies, we carried out Gm typing of ‘receptor‐purified’ IgG from patients with active Graves' disease and controls. The results were compared to those of serum, total IgG and IgG which failed to attach to TSH‐R. We found that in five out of seven Gm heterozygote patients studied the receptor‐purified antibodies were restricted to the products of one haplotype compared to three out of five similar controls. Such eluted antibodies were biologically active. Similar results in terms of immunogenetic restriction and activity were obtained when F(ab)2 preparations were used. An unexpected finding was that sera and IgG from normal persons attached to thyroid membranes and that the attachment occurred via F(ab)2. Normal whole serum and ‘receptor‐purified’ IgG and F(2 inhibited TSH binding in the receptor assay; however, this inhibition showed no specificity for TSH‐R.