Journal Article

Modulation of autoantibody production by mycophenolate mofetil: effects on the development of SLE in (NZB×NZW)F<sub>1</sub> mice

Ma Angeles Ramos, Celestino Piñera, Ma Angeles Setién, Luis Buelta, Ma Angeles de Cos, Angel‐Luis M. de Francisco, Ramón Merino and Manuel Arias

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 18, issue 5, pages 878-883
Published in print May 2003 | ISSN: 0931-0509
Published online May 2003 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfg034
Modulation of autoantibody production by mycophenolate mofetil: effects on the development of SLE in (NZB×NZW)F1 mice

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Background. Mycophenolate mofetil (MMF) has been successfully used to improve or prevent the development of systemic lupus erythematosus (SLE) in both humans and in several lupus‐prone mice. In the present study, we evaluated mechanisms through which MMF may exert its therapeutic effect on the development of systemic autoimmunity.

Methods. (NZB×NZW)F1 female mice were continuously treated with 100 mg/kg/day (high dose) or 30 mg/kg/day (low dose) MMF beginning at 3 months of age. The development of an autoimmune syndrome was evaluated by measuring immunoglobulin (Ig) isotypes of autoantibodies and their levels, as well as by evaluating immunopathological kidney abnormalities and mortality curves.

Results. At both doses, MMF efficiently modulated the development of SLE. Although the higher dose of MMF directly inhibited the production of autoantibodies, 30 mg/kg/day MMF promoted qualitative but not quantitative changes in autoantibodies in (NZB×NZW)F1 female mice. These qualitative changes were manifested as a selective reduction in total or antigen‐specific IgG2a antibody levels.

Conclusions. The mechanisms through which MMF controls the development of SLE in (NZB×NZW)F1 females is highly dependent upon immunosuppressor dose. Interestingly, lower dose MMF selectively reduced IgG2a antibody levels, suggesting that this dose may modulate TH1 CD4+ activity.

Keywords: autoantibodies; mycophenolate mofetil; (NZB×NZW)F1 mice; systemic lupus erythematosus

Journal Article.  3561 words.  Illustrated.

Subjects: Nephrology

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