title: Differential effects of cyclophosphamide and mycophenolate mofetil on cellular and serological parameters in patients with systemic lupus erythematosus.
abstract: BACKGROUND
  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.
authors.affiliation: Division of Rheumatology and Clinical Immunology/ Department of Internal Medicine D, University Hospital Münster, Albert-Schweitzer-Campus 1, Building A1, 48149, Münster, Germany. fassbinder@st-josef-stift.de.
authors.forename: Till
authors.initials: T
authors.lastname: Fassbinder
authors.affiliation: Division of Rheumatology and Clinical Immunology/ Department of Internal Medicine D, University Hospital Münster, Albert-Schweitzer-Campus 1, Building A1, 48149, Münster, Germany. ute.saunders@ukmuenster.de.
authors.forename: Ute
authors.initials: U
authors.lastname: Saunders
authors.affiliation: Division of Rheumatology and Clinical Immunology/ Department of Internal Medicine D, University Hospital Münster, Albert-Schweitzer-Campus 1, Building A1, 48149, Münster, Germany. eva.mickholz@ukmuenster.de.
authors.forename: Eva
authors.initials: E
authors.lastname: Mickholz
authors.affiliation: Division of Rheumatology and Clinical Immunology/ Department of Internal Medicine D, University Hospital Münster, Albert-Schweitzer-Campus 1, Building A1, 48149, Münster, Germany. elisabeth.jung@ukmuenster.de.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Jung
authors.affiliation: Division of Rheumatology and Clinical Immunology/ Department of Internal Medicine D, University Hospital Münster, Albert-Schweitzer-Campus 1, Building A1, 48149, Münster, Germany. heidemarie.becker@ukmuenster.de.
authors.forename: Heidemarie
authors.initials: H
authors.lastname: Becker
authors.affiliation: Center for Laboratory Medicine, University Hospital Münster, Albert-Schweitzer-Campus 1, Building A1, 48149, Münster, Germany. bernhard.schlueter@ukmuenster.de.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Schlüter
authors.affiliation: Division of Rheumatology and Clinical Immunology/ Department of Internal Medicine D, University Hospital Münster, Albert-Schweitzer-Campus 1, Building A1, 48149, Münster, Germany. a.jacobi@mhb-fontane.de.|Division of Rheumatology and Clinical Immunology, Brandenburg Medical School, Fehrbelliner Str. 38, 16816, Neuruppin, Germany. a.jacobi@mhb-fontane.de.
authors.forename: Annett Marita
authors.initials: AM
authors.lastname: Jacobi
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D003430:Cross-Sectional Studies; D003520:Cyclophosphamide / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008180:Lupus Erythematosus, Systemic / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D010950:Plasma Cells / Q000166:cytology / Q000187:drug effects*; D012016:Reference Values; D018570:Risk Assessment; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D009173:Mycophenolic Acid