Anti-idiotype and immunosuppressant treatment of murine lupus

Author:

MORLAND C1,MICHAEL J1,ADU D1,KIZAKI T2,HOWIE A J2,MORGAN A3,STAINES N A3

Affiliation:

1. Renal Research Laboratory, Queen Elizabeth Hospital, Edgbaston, Birmingham, England

2. Department of Pathology, University of Birmingham Medical School, Birmingham, England

3. Immunology Section, Kings College, London, England

Abstract

SUMMARY The effect of the administration of a xenogeneic anti-idiotype antibody (anti-Id33) to a cross-reactive idiotype (Id33) present on anti-dsDNA antibody was examined in 6-week-old (NZB/NZW) F1 (BWF1) female mice. The administration of anti-Id33 led to a transient reduction in immunoglobulins expressing Id33, followed by a rise at 30 and 34 weeks that was significantly higher than in untreated mice (P<0.05). Likewise, anti-dsDNA antibody levels were significantly higher at 10 and 18 weeks than in untreated mice (P<0.0l). No differences were seen in survival to 40 weeks, proteinuria or the severity of glomerulonephritis. Concurrent administration of cyclosporin A(CyA) with anti-Id33 markedly ameliorated glomerular injury and proteinuria and improved survival. By contrast, glomerular injury, proteinuria and survival were worse in mice treated with cyclophosphamide plus anti-Id33, compared with untreated mice. Neither CyA nor cyclophosphamide treatment, when given with anti-Id33 altered serum levels of anti-dsDNA, anti-ssDNA or Id33+ immunoglobin, compared with untreated mice. The different effects of CyA and cyclophosphamide on T lymphocytes and their discrepant effects on glomerular injury when given with anti-Id33 in this model lead us to postulate a role for T lymphocytes in the glomerular injury of BWF1 lupus.

Publisher

Oxford University Press (OUP)

Subject

Immunology,Immunology and Allergy

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