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Arthritis Res Ther. 2012;14(3):R110.

Mycophenolic acid counteracts B cell proliferation and plasmablast formation in patients with systemic lupus erythematosus.

Author information

  • 1Rheumatology and Clinical Immunology Unit of the Department of Internal Medicine D, University Hospital Münster, Albert Schweitzer Str. 33, 48149 Münster, Germany. SebastianEickenberg@web.de

Abstract

INTRODUCTION:

Clinical trials revealed a high efficacy of mycophenolate mofetil (MMF)in inducing and maintaining remission in patients with class III-V-lupus nephritis. Also extrarenal manifestations respond to MMF treatment. However, few attempts have been undertaken to delineate its mechanism of action in systemic lupus erythematosus (SLE) a disease characterized by enhanced B cell activation.

METHODS:

Clinical and paraclinical parameters of 107 patients with SLE were recorded consecutively and analyzed retrospectively. Patients were divided into treatment groups (MMF: n=39, azathioprine (AZA) n=30 and controls without immunosuppressive therapy n=38). To further delineate the effect of mycophenolic acid (MPA) on naive and memory B cells in vitro assays were performed.

RESULTS:

Although patients taking AZA flared more frequently than patients on MMF or controls, the analysis of clinical parameters did not reveal significant differences.However, profound differences in paraclinical parameters were found. B cell frequencies and numbers were significantly higher in patients taking MMF compared to those on AZA but lower numbers and frequencies of plasmablasts were detected compared to AZA-treated patients or controls. Notably, MMF treatment was associated with a significantly higher frequency and number of transitional B cells as well as naive B cells compared to AZA treatment. Differences in T cell subsets were not significant. MPA abrogated in vitro proliferation of purified B cells completely but had only moderate impact on B cell survival.

CONCLUSIONS:

The thorough inhibition of B cell activation and plasma cell formation by MMF might explain the favorable outcomes of previous clinical trials in patients with SLE, since enhanced B cell proliferation is a hallmark of this disease.

PMID:
22571761
[PubMed - indexed for MEDLINE]
PMCID:
PMC4060361
Free PMC Article

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