title: Pulsed monoclonal antibody treatment and autoimmune thyroid disease in multiple sclerosis.
abstract: 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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.affiliation: University of Cambridge Neurology Unit, University of Cambridge, UK. alasdair_coles@hotmail.com
authors.forename: A J
authors.initials: AJ
authors.lastname: Coles
authors.forename: M
authors.initials: M
authors.lastname: Wing
authors.forename: S
authors.initials: S
authors.lastname: Smith
authors.forename: F
authors.initials: F
authors.lastname: Coraddu
authors.forename: S
authors.initials: S
authors.lastname: Greer
authors.forename: C
authors.initials: C
authors.lastname: Taylor
authors.forename: A
authors.initials: A
authors.lastname: Weetman
authors.forename: G
authors.initials: G
authors.lastname: Hale
authors.forename: V K
authors.initials: VK
authors.lastname: Chatterjee
authors.forename: H
authors.initials: H
authors.lastname: Waldmann
authors.forename: A
authors.initials: A
authors.lastname: Compston
mesh_terms: D000328:Adult; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000008:administration & dosage / Q000009:adverse effects*; D015703:Antigens, CD / Q000276:immunology; D000951:Antigens, Neoplasm; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D016175:B-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D000074301:CD52 Antigen; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006023:Glycoproteins / Q000276:immunology; D006111:Graves Disease / Q000139:chemically induced / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage / Q000009:adverse effects; D020528:Multiple Sclerosis, Chronic Progressive / Q000188:drug therapy* / Q000276:immunology; D020551:Pulse Therapy, Drug; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D013967:Thyroiditis, Autoimmune / Q000139:chemically induced* / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D018501:Antirheumatic Agents; D015704:CD4 Antigens; D000074301:CD52 Antigen; C000613862:CD52 protein, human; D006023:Glycoproteins; D018124:Receptors, Tumor Necrosis Factor; D000074323:Alemtuzumab; D008775:Methylprednisolone