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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.    Conclusion  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.

Distinct Effects of Methotrexate and Etanercept on the B Cell Compartment in Patients With Juvenile Idiopathic Arthritis