title: Mycophenolic acid counteracts B cell proliferation and plasmablast formation in patients with systemic lupus erythematosus.
abstract: BACKGROUND
  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.affiliation: Rheumatology and Clinical Immunology Unit of the Department of Internal Medicine D, University Hospital Münster, Albert Schweitzer Str. 33, 48149 Münster, Germany. SebastianEickenberg@web.de
authors.forename: Sebastian
authors.initials: S
authors.lastname: Eickenberg
authors.forename: Eva
authors.initials: E
authors.lastname: Mickholz
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Jung
authors.forename: Jerzy-Roch
authors.initials: JR
authors.lastname: Nofer
authors.forename: Hermann J
authors.initials: HJ
authors.lastname: Pavenstadt
authors.forename: Annett M
authors.initials: AM
authors.lastname: Jacobi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001379:Azathioprine / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000627:therapeutic use*; D010950:Plasma Cells / Q000187:drug effects; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D001379:Azathioprine