Terminal complement complexes and C1/C1 inhibitor complexes in autoimmune thyroid disease.

The potential role of complement activation and the membrane attack complex in the pathogenesis of Graves' disease and Hashimoto's thyroiditis has been investigated by measuring serum concentrations of the C1r-C1s-C1 inhibitor complex (C1/C1-inh) and the terminal complement complex (TCC), and by studying the binding to thyroid tissue of monoclonal and polyclonal antibodies against TCC neoantigens. Serum C1/C1-inh and TCC concentrations were significantly increased in 29 patients with untreated Graves' disease compared with 47 healthy subjects (P less than 0.001 for both), and decreased significantly after carbimazole treatment in 18 of these patients for whom post-treatment samples were available (P less than 0.01 and P less than 0.02, respectively). The serum TCC concentration, but not that of C1/C1-inh, was also significantly increased in 15 patients with Hashimoto's thyroiditis compared with the 47 healthy subjects (P less than 0.001). TCCs were identified by immunohistochemical staining around the thyroid follicles in thyroidectomy specimens from patients with Graves' disease (six out of six) and Hashimoto's thyroiditis (two out of two); normal thyroid tissue from two subjects showed no staining. These results suggest a role for complement, in particular the membrane attack complex in the pathogenesis of autoimmune thyroid disease.