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Mycophenolic acid counteracts B cell proliferation and plasmablast formation in
patients with systemic lupus erythematosus
#MMPMID22571761
Eickenberg S
; Mickholz E
; Jung E
; Nofer JR
; Pavenstadt HJ
; Jacobi AM
Arthritis Res Ther
2012[]; 14
(3
): R110
PMID22571761
show ga
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.
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