TY - JOUR
T1 - Immunotherapy of experimental autoimmune myasthenia gravis
T2 - Selective effects of CTLA4Ig and synergistic combination with an IL2-Diphtheria toxin fusion protein
AU - McIntosh, Kevin R.
AU - Linsley, Peter S.
AU - Bacha, Patricia A.
AU - Drachman, Daniel B.
N1 - Funding Information:
We are grateful to Sheila Moran, B.S. for expert technical assistance. This is supported by grants from the National Institutes of Health # 1 R01 NS23719, Muscular Dystrophy Association, and Bristol-Myers Squibb; and gifts from the C. Walder Parke family and the Ann and Donald Brown Foundation.
Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 1998/7/1
Y1 - 1998/7/1
N2 - We examined the effects of CTLA4Ig treatment in an experimental model of myasthenia gravis (EAMG) induced by immunizing Lewis rats with purified Torpedo acetylcholine receptor (AChR). During a primary response, CTLA4Ig treatment inhibited AChR antibody production profoundly, and induced a shift of AChR antibody isotypes from the normally predominant IgG2 isotype pattern toward an IgG1 response. Challenge of rats previously treated with CTLA4Ig produced markedly lower AChR antibody responses compared to untreated controls, persistent inhibition of the IgG2b isotype, and no development of EAMG. Treatment of a secondary AChR response with CTLA4Ig or with DAB389IL2 (which kills lymphocytes expressing IL2 receptors) inhibited AChR antibody responses, and clinical EAMG moderately. In contrast, combined treatment with CTLA4Ig plus DAB389IL2 strikingly inhibited AChR antibody levels, and completely prevented EAMG. Our results suggest that the therapeutic benefit of CTLA4Ig may be due to overall inhibition of AChR antibody production as well as a shift in the antibody isotype repertoire.
AB - We examined the effects of CTLA4Ig treatment in an experimental model of myasthenia gravis (EAMG) induced by immunizing Lewis rats with purified Torpedo acetylcholine receptor (AChR). During a primary response, CTLA4Ig treatment inhibited AChR antibody production profoundly, and induced a shift of AChR antibody isotypes from the normally predominant IgG2 isotype pattern toward an IgG1 response. Challenge of rats previously treated with CTLA4Ig produced markedly lower AChR antibody responses compared to untreated controls, persistent inhibition of the IgG2b isotype, and no development of EAMG. Treatment of a secondary AChR response with CTLA4Ig or with DAB389IL2 (which kills lymphocytes expressing IL2 receptors) inhibited AChR antibody responses, and clinical EAMG moderately. In contrast, combined treatment with CTLA4Ig plus DAB389IL2 strikingly inhibited AChR antibody levels, and completely prevented EAMG. Our results suggest that the therapeutic benefit of CTLA4Ig may be due to overall inhibition of AChR antibody production as well as a shift in the antibody isotype repertoire.
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U2 - 10.1016/S0165-5728(98)00071-X
DO - 10.1016/S0165-5728(98)00071-X
M3 - Article
C2 - 9670855
AN - SCOPUS:0032126158
VL - 87
SP - 136
EP - 146
JO - Advances in Neuroimmunology
JF - Advances in Neuroimmunology
SN - 0165-5728
IS - 1-2
ER -