HIGH-FREQUENCY OF B-CELLS CAPABLE OF PRODUCING ANTITHYROTROPIN RECEPTOR ANTIBODIES IN PATIENTS WITH GRAVES-DISEASE

Hyperthyroidism in Graves' disease (GD) is mediated by antibodies to t he thyrotropin receptor (TSHr). Patients that go into remission show a decline in antibody titer. However, upon cessation of treatment with anti-thyroid drugs a significant proportion of patients relapse and TS Hr antibodies (TSHrAb) are present in their circulation. This suggests that B cells capable of producing TSHrAb persist despite treatment. T o determine the frequency of these cells, B cells from six patients wi th GD and four healthy controls were infected with Epstein-Barr virus and cultured in 96-well plates at varying cell concentrations. A highe r frequency of B cells capable of producing TSHrAbs was detected in pa tients with GD, relative to normal controls. For example, at 2 x 10(5) eels per well, 100% of wells containing cells from either patients wi th GD or controls were positive for immunoglobulin (Ig) production. In contrast, 27% of the wells containing cells from Graves' patients, an d only 3% from controls, were positive for TSHrAb. Higher titers of TS HrAbs were produced in cultures containing lymphocytes from patients w ith GD and were predominantly of IgG isotype. All patients with GD who had high thyrotropin binding inhibitory immunoglobulins also had high er frequencies of TSHr-specific B cells. These findings show that TSHr Ab-producing B cells are present at a higher frequency in the peripher al circulation of patients with GD. (C) 1994 Academic Press, Inc.