title: Distinct effects of methotrexate and etanercept on the B cell compartment in patients with juvenile idiopathic arthritis.
abstract: OBJECTIVE
  B cells have been shown to play an important role in the pathogenesis of rheumatoid arthritis and juvenile idiopathic arthritis (JIA). Current treatments include the disease-modifying antirheumatic drugs methotrexate (MTX) and tumor necrosis factor α inhibition with etanercept. This study was undertaken to determine how these drugs influence the B cell compartment in patients with JIA.
  
  
  METHODS
  B cell subpopulations and follicular helper T (Tfh) cells in the peripheral blood of JIA patients were investigated by multicolor flow cytometry. Serum immunoglobulin and BAFF levels were determined by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  There was a significant decrease in transitional B cells and significantly lower serum immunoglobulin levels in patients receiving MTX than in untreated patients and those receiving etanercept. In contrast, etanercept treatment had no effect on most of the B cell subpopulations, but resulted in significantly lower BAFF levels and increased numbers of Tfh cells. Thus, our findings indicate an unexpected and previously unknown direct effect of low-dose MTX on B cells, whereas etanercept had a more indirect influence.
  
  
  CONCLUSIONS
  Our results contribute to a better understanding of the potency of MTX in autoantibody-mediated autoimmune disease and present a possible mechanism of prevention of the development of drug-induced antibodies to biologic agents. The finding that MTX and etanercept affect the B cell compartment differently supports the notion that combination therapy with etanercept and MTX is more effective than monotherapy.
authors.affiliation: Hannover Medical School, Hannover, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Glaesener
authors.forename: Tâm D
authors.initials: TD
authors.lastname: Quách
authors.forename: Nils
authors.initials: N
authors.lastname: Onken
authors.forename: Frank
authors.initials: F
authors.lastname: Weller-Heinemann
authors.forename: Frank
authors.initials: F
authors.lastname: Dressler
authors.forename: Hans-Iko
authors.initials: HI
authors.lastname: Huppertz
authors.forename: Angelika
authors.initials: A
authors.lastname: Thon
authors.forename: Almut
authors.initials: A
authors.lastname: Meyer-Bahlburg
mesh_terms: D000293:Adolescent; D018501:Antirheumatic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001171:Arthritis, Juvenile / Q000188:drug therapy* / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects*; D002648:Child; D000068800:Etanercept; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008727:Methotrexate / Q000494:pharmacology* / Q000627:therapeutic use; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D000068800:Etanercept; D008727:Methotrexate