Pulsed monoclonal antibody treatment and autoimmune thyroid disease in multiple sclerosis.

Journal article

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.

Authors: Coles, A; Wing, M; Smith, S; Coraddu, F; Greer, S

• Publication status: Published
• Journal: Lancet
• Volume: 354
• Issue: 9191
• Pages: 1691-1695
• Publication date: 1999-11-01
• DOI: 10.1016/s0140-6736(99)02429-0
• EISSN: 1474-547X
• ISSN: 0140-6736
• Language: English
• Keywords: Drug Administration Schedule; Th1 Cells; T-Lymphocyte Subsets; Follow-Up Studies; Receptors, Tumor Necrosis Factor; Antibodies, Monoclonal; Adult; Antibodies, Monoclonal, Humanized; B-Lymphocyte Subsets; Antibodies, Neoplasm; Male; Antigens, Neoplasm; Thyroiditis, Autoimmune; Lymphocyte Activation; Humans; Glycoproteins; Antigens, CD4; Graves Disease; Female; Antirheumatic Agents; Methylprednisolone; Pulse Therapy, Drug; Multiple Sclerosis, Chronic Progressive; Antigens, CD