Differential effects of cyclophosphamide and mycophenolate mofetil on cellular and serological parameters in patients with systemic lupus erythematosus

Till Fassbinder, Ute Saunders, Eva Mickholz, Elisabeth Jung, Heidemarie Becker, Bernhard Schlüter, Annett Marita Jacobi, Till Fassbinder, Ute Saunders, Eva Mickholz, Elisabeth Jung, Heidemarie Becker, Bernhard Schlüter, Annett Marita Jacobi

Abstract

Introduction: Disease activity and therapy show an impact on cellular and serological parameters in patients with systemic lupus erythematosus (SLE). This study was performed to compare the influence of mycophenolate mofetil (MMF) and cyclophosphamide (CYC) therapy on these parameters in patients with flaring, organ-threatening disease.

Methods: SLE patients currently receiving CYC (n = 20), MMF (n = 25) or no immunosuppressive drugs (n = 22) were compared using a cross-sectional design. Median disease activity and daily corticosteroid dose were similar in these treatment groups. Concurrent medication, organ manifestations, and disease activity were recorded, and cellular and serological parameters were determined by routine diagnostic tests or flow cytometric analysis. In addition follow-up data were obtained from different sets of patients (CYC n = 24; MMF n = 23).

Results: Although both drugs showed a significant effect on disease activity and circulating B cell subsets, only MMF reduced circulating plasmablasts and plasma cells as well as circulating free light chains within three months of induction therapy. Neither MMF nor CYC were able to reduce circulating memory B cells. MMF lowered IgA levels more markedly than CYC. We did not observe a significant difference in the reduction of IgG levels or anti-dsDNA antibodies comparing patients receiving MMF or CYC. In contrast to MMF, induction therapy with CYC was associated with a significant increase of circulating CD8+ effector T cells and plasmacytoid dendritic cells (PDCs) after three months.

Conclusions: The results indicate differences between MMF and CYC with regard to the mechanism of action. MMF, but not CYC, treatment leads to a fast and enduring reduction of surrogate markers of B cell activation, such as circulating plasmablasts, plasma cells and free light chains but a comparable rate of hypogammaglobulinemia.

Figures

Figure 1
Figure 1
Influence of an induction therapy with mycophenolate mofetil (MMF) or cyclophosphamide (CYC) on plasmablast and plasma cell counts. CD27++CD38++HLADRhigh plasmablast (A) and CD27++CD38++HLADRlow plasma cell counts (C) prior to and approximately 16 and 31 weeks after start of induction therapy with MMF. CD27++CD38++HLADRhigh plasmablast (B) and CD27++CD38++HLADRlow plasma cell counts (D) prior to and approximately 15 weeks after start of induction therapy with CYC. Statistical analyses were performed using the Wilcoxon’s matched pairs signed rank test and P-values <0.05 were considered significant.
Figure 2
Figure 2
Influence of induction therapy with mycophenolate mofetil (MMF) and cyclophosphamide (CYC) on free light chain (FLC) levels. Levels of free kappa light chains (FLCkappa) (A) and free lambda light chains (FLClambda) (C) prior to and approximately 16 and 31 weeks after start of induction therapy with MMF. Levels of free kappa light chains (FLCkappa) (B) and free lambda light chains (FLClambda) (D) prior to and approximately 15 weeks after start of induction therapy with CYC. Statistical analyses were performed using the Wilcoxon’s matched pairs signed rank test and P-values <0.05 were considered significant.

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