Serum BAFF Concentrations in Patients with Graves' Disease and Orbitopathy before and after Immunosuppressive Therapy

Introduction: B cells are known to play a key role in the pathogenesis of autoimmune disease. B lymphocyte activating factor (BAFF), a member of TNF family, promotes autoantibody production by increasing B cell survival and proliferation. Serum BAFF concentrations have been found to be increased in systemic lupus erythematosus, rheumatoid arthritis, and Sjogren's syndrome. Objective: We have measured serum BAFF concentrations in patients with Graves' disease (GD) with or without Graves' orbitopathy (GO) and in active GO in relation to immunosuppressive treatment. Methods: Forty-two patients and nine normal controls were studied. Thirty-four patients had GO, which was active in 23. Of these, nine were treated with rituximab (RTX) and 14 with iv methylprednisolone (MP). Serum BAFF concentrations were measured at baseline in all patients, at peripheral B cell depletion and repopulation after RTX, and after therapy with MP. Results: Serum basal BAFF concentrations in GD patients were significantly higher when compared with normal controls (P = 0.0001), and no difference was observed in those with active or inactive GO. Serum BAFF concentrations were also significantly correlated with serum antithyroglobulin antibodies (P = 0.04) but not with sex, age, smoking habits, therapy for thyroid disease, and serum antithyroperoxidase antibodies and TSH receptor antibodies. After RTX, there was an increase of serum BAFF concentrations at the time of B cell depletion (P = 0.02) but also at B cell repopulation (P = 0.04). In patients treated with MP, serum BAFF concentrations decreased significantly after therapy (P < 0.01). Conclusions: We report that serum BAFF concentrations are elevated in patients with GD, in whom hyperthyroidism is known to be based on a B-cell-driven pathophysiological mechanism. In active GO, BAFF further increases after therapy with RTX as a consequence of the B cell depletion per se. The decrease of serum BAFF after iv steroids suggests that MP may exert an immunosuppressive effect by modifying B-cell-derived immune reactions. (J Clin Endocrinol Metab 97: E755-E759, 2012)