Antineutrophil Autoantibodies in Graves' Disease

The hyperthyroidism of Graves' disease may be caused by autoantibodies to thyrotropin (TSH) receptors. We have found that patients with this disease have autoantibodies to neutrophils as well, which can be displaced by TSH. Using a radiochemical opsonic assay, we found serum antibodies against homologous neutrophils in 6 of 11 Graves' patients. With a staphylococcal protein A-binding assay, we detected circulating antibodies to homologous neutrophils in 10 of 20 patients, while finding cellbound antibody on autologous neutrophils in 7 of 8 (including 2 with negative serum tests). Use of human '25I-TSH in a radioligand binding assay revealed that TSH bound to neutrophils rapidly (maximum binding within 10 min at 220C, pH 7.4), specifically (<20% nonspecific binding), and reversibly. Adding TSH to the radiochemical assay resulted in a dosedependent inhibition of opsonic antibody activity in serum from patients with Graves' disease. In contrast, TSH did not inhibit antibody activity of serum from patients with immune neutropenia not associated with thyroid disease. Our findings suggest a basis for the association of Graves' disease with neutropenia. Furthermore, the discovery of such antineutrophil antibodies in Graves' disease permits detection of cell-bound antibody when free antibody is not present.