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

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.

• Authors: Sebastian Eickenberg, Eva Mickholz, Elisabeth Jung, Jerzy-Roch Nofer, Hermann J Pavenstadt, Annett M Jacobi
• Journal: Arthritis research & therapy (Arthritis Res Ther) Vol. 14 Issue 3 Pg. R110 ( 2012) ISSN: 1478-6362 [Electronic] England
• PMID: 22571761 (Publication Type: Journal Article)

Chemical References

• Immunosuppressive Agents
• Mycophenolic Acid
• Azathioprine

Topics

• Adolescent
• Adult
• Aged
• Azathioprine (therapeutic use)
• B-Lymphocytes (cytology, drug effects)
• Cell Proliferation (drug effects)
• Female
• Flow Cytometry
• Humans
• Immunosuppressive Agents (therapeutic use)
• Lupus Erythematosus, Systemic (drug therapy, immunology)
• Lymphocyte Activation (drug effects)
• Male
• Middle Aged
• Mycophenolic Acid (therapeutic use)
• Plasma Cells (drug effects)
• Retrospective Studies
• Young Adult