Studies of possible antiidiotypic control mechanisms in Graves' disease

Serum from 55 patients with active Graves' disease and 55 patients who had received successful treatment (in whom the disease was inactive) were examined for the presence of possible antiidiotypic antibodies with an enzyme-linked immunosorbent assay (ELISA) for anti-F(ab')2. Murine IgG monoclonal antibodies (Mabs) against human thyroid-stimulating hormone (TSH) and human TSH receptors were also used as antigens in parallel ELISA assays. Patients with active and patients with inactive Graves' disease showed elevations of IgG anti-F(ab')2 antibodies when compared with normal controls. Similarly, both active and inactive Graves' disease sera showed higher levels of IgG anti-LE4, a mouse Mab to human TSH, than was seen with normal controls. However, F(ab')2 isolated from sera reacting with LE4 in the ELISA did not inhibit binding of the LE4 Mab with labeled TSH in a fluid phase competition assay. Patients with inactive Graves' disease showed higher ELISA reactivity with two different murine anti-TSH receptor Mabs than was recorded with either active Graves' or normal controls. A rough inverse correlation was noted between strongly positive ELISA reactions against these two Mabs with anti-TSH receptor specificity and the ability of immunoglobulins from inactive Graves' sera to stimulate increases in cyclic adenosine monophosphate (cAMP) in the normal rat thyroid cell line assay. Untreated Graves' sera showing high cAMP release only rarely showed elevated ELISA reactivity against Mabs with anti-TSH receptor activity.