Hannover Medical School, Hannover, Germany.
Arthritis Rheumatol. 2014 Sep;66(9):2590-600. doi: 10.1002/art.38736.
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.
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.
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.
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.
已证实 B 细胞在类风湿关节炎和幼年特发性关节炎（JIA）的发病机制中发挥重要作用。目前的治疗方法包括甲氨蝶呤（MTX）等疾病修饰抗风湿药物和依那西普等肿瘤坏死因子α抑制剂。本研究旨在确定这些药物如何影响 JIA 患者的 B 细胞群。
通过多色流式细胞术检测 JIA 患者外周血中的 B 细胞亚群和滤泡辅助 T（Tfh）细胞。通过酶联免疫吸附试验测定血清免疫球蛋白和 BAFF 水平。
与未治疗患者和接受依那西普治疗的患者相比，接受 MTX 治疗的患者过渡性 B 细胞显著减少，血清免疫球蛋白水平显著降低。相比之下，依那西普治疗对大多数 B 细胞亚群没有影响，但导致 BAFF 水平降低和 Tfh 细胞数量增加。因此，我们的研究结果表明，低剂量 MTX 对 B 细胞具有意想不到的、以前未知的直接作用，而依那西普的影响则更为间接。
我们的研究结果有助于更好地理解 MTX 在自身抗体介导的自身免疫性疾病中的作用，并提出了预防生物制剂药物诱导抗体产生的可能机制。MTX 和依那西普对 B 细胞群的影响不同，这一发现支持依那西普和 MTX 联合治疗比单一治疗更有效的观点。
