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

Abstract

IntroductionDisease 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.MethodsSLE 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).ResultsAlthough 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.ConclusionsThe 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-015-0603-8) contains supplementary material, which is available to authorized users.

Management of interstitial lung disease associated with connective tissue disease

“…In a cohort study of 45 patients with SLE without ILD who were treated with mycophenolate mofetil or cyclophosphamide, rates of hypogammaglobulinemia were similar for both treatments, although IgA levels were significantly lower in those treated with mycophenolate mofetil. 107 No data on subsequent development of ILD were provided.…”

Chemoprotective effect of ascorbic acid on cyclophosphomide induced oral toxicity

“…[8][9][10] Oral mucositis is a common, debilitating complication of CTX therapy; furthermore, patients with damaged oral mucosa and reduced immunity are prone to opportunistic infections. 11 The most common types of treatment for oral mucositis are topical antimicrobial agents, non-alcoholic mouth washes, supplementary amino acids, cryotherapy, low-level laser treatment, herbs and vitamins.…”

Lupus pathobiology based on genomics

“…CYC exerts its cytotoxic effect on predominantly B-lymphocytes by crosslinking DNA with alkyl groups, thus inhibiting DNA replication. Plasmablasts and plasma cells are not affected by cyclophosphamide (Miller and Cole 1967; Fassbinder et al 2015); however, naïve B-cells are rapidly depleted (Fassbinder et al 2015). Azathioprine (AZA) used in maintenance therapy for SLE, is a prodrug for 6-mercaptopurine, a purine analog impeding DNA synthesis via several enzymes including inosine monophosphate dehydrogenase (IMPDH).…”

“…MMF is a prodrug of mycophenolic acid which reversibly inhibits IMPDH, preferentially the type-II form of the enzyme that is upregulated in activated lymphocytes, leading to cell cycle arrest (Lee et al 1985). Plasmablasts and plasma cells were significantly reduced in peripheral blood of MMF-treated patients with subsequent effect on antibody production (Fassbinder et al 2015; Eickenberg et al 2012). In contrast to CYC, T-cell subsets are unaffected by both MMF and AZA.…”