Pulsed monoclonal antibody treatment and autoimmune thyroid disease in multiple sclerosis
AJ Coles, M Wing, S Smith, F Coraddu, S Greer… - The Lancet, 1999 - thelancet.com
The Lancet, 1999•thelancet.com
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 …
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 …
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.
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