Pulsed monoclonal antibody treatment and autoimmune thyroid disease in multiple sclerosis
自身抗体
甲状腺
甲状腺炎
自身免疫
作者
Alasdair Coles,M. G. Wing,Sheila I. Smith,Francesca Coraddu,Sandra Greer,Craig J. Taylor,Anthony P. Weetman,Geoff Hale,V. Krishna K. Chatterjee,Herman Waldmann,Alastair Compston
Summary Background Multiple sclerosis results from T-cell-dependent inflammatory demyelination of the central nervous system. Our objective was long-term suppression of inflammation with short-term monoclonal antibody treatment. Methods We depleted 95% of circulating lymphocytes in 27 patients with multiple sclerosis by means of a 5-day pulse of the humanised anti-CD52 monoclonal antibody, Campath-1H. Clinical and haematological consequences of T-cell depletion, and in-vitro responses of patients' peripheral-blood mononuclear cells were analysed serially for 18 months after treatment. Findings Radiological and clinical markers of disease activity were significantly decreased for at least 18 months after treatment. However, a third of patients developed antibodies against the thyrotropin receptor and carbimazole-responsive autoimmune hyperthyroidism. The depleted peripheral lymphocyte pool was reconstituted with cells that had decreased mitogen-induced proliferation 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.