Pulsed monoclonal antibody treatment and autoimmune thyroid disease in multiple sclerosis

Background Multiple sclerosis results from T-cell-dependent inflammatory de myelination of the central nervous system. Our objective was long-term supp ression of inflammation with short-term monoclonal antibody treatment. Methods We depleted 95% of circulating lymphocytes in 27 patients with mult iple sclerosis by means of a 5-day pulse of the humanised anti-CD52 monoclo nal antibody, Campath-1H, Clinical and haematological consequences of T-cel l depletion, and in-vitro responses of patients' peripheral-blood mononucle ar cells were analysed serially for 18 months after treatment. Findings Radiological and clinical markers of disease activity were signifi cantly decreased for at least 18 months after treatment. However, a third o f patients developed antibodies against the thyrotropin receptor and carbim azole-responsive autoimmune hyperthyroidism. The depleted peripheral lympho cyte pool was reconstituted with cells that had decreased mitogen-induced p roliferation and interferon gamma secretion in vitro, Interpretation Campath-1H causes the immune response to change from the Th1 phenotype, suppressing multiple sclerosis disease activity, but permitting the generation of antibody-mediated thyroid autoimmunity.