Pulsed monoclonal antibody treatment and autoimmune thyroid disease in multiple sclerosis.
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.
Coles
A J
AJ
University of Cambridge Neurology Unit, University of Cambridge, UK. alasdair_coles@hotmail.com
Wing
M
M
Smith
S
S
Coraddu
F
F
Greer
S
S
Taylor
C
C
Weetman
A
A
Hale
G
G
Chatterjee
V K
VK
Waldmann
H
H
Compston
A
A
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
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