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类风湿关节炎患者的 T 细胞受体 BV 家族中克隆性扩张可被 TNFα 抑制剂依那西普和英夫利昔单抗治疗所减少。

Clonal expansions in selected TCR BV families of rheumatoid arthritis patients are reduced by treatment with the TNFα inhibitors etanercept and infliximab.

机构信息

Department of Medicine II, University of Leipzig, Johannisallee 30, Leipzig, Germany.

出版信息

Rheumatol Int. 2011 Aug;31(8):1023-9. doi: 10.1007/s00296-010-1402-9. Epub 2010 Mar 20.

Abstract

Clonal expansions of autoreactive CD4+ T cells are frequently present in patients with rheumatoid arthritis (RA) and are stable over long periods of time. This study was undertaken to investigate the influence of anti-TNFα treatment on such clonal expansions in the peripheral CD4+ T-cell compartment. TNFα inhibiting therapies significantly reduced the total number of expanded clonotypes. This effect was mainly observed in clonal expansions in the BV6 family, while in clonal expansions of the BV14 family no such effect was seen. No change in the percentage of CD4+ CD28 null T cells was observed. Serum concentrations of the pro-homeostatic cytokine IL-7 were found to increase in patients responding TNFα-inhibiting therapy. These data argue for a normalization of adaptive immune mechanisms under TNFα inhibiting therapies, which may be secondary to the control of inflammation but contribute to the efficacy of cytokine blockade therapy.

摘要

自身反应性 CD4+T 细胞的克隆扩增在类风湿关节炎(RA)患者中经常存在,并在很长一段时间内保持稳定。本研究旨在探讨抗 TNFα 治疗对周围 CD4+T 细胞区室中这种克隆扩增的影响。TNFα 抑制疗法显著减少了扩增克隆型的总数。这种效应主要发生在 BV6 家族的克隆扩增中,而在 BV14 家族的克隆扩增中则没有观察到这种效应。CD4+CD28 缺失 T 细胞的百分比没有变化。在对 TNFα 抑制治疗有反应的患者中,发现促同型细胞因子 IL-7 的血清浓度增加。这些数据表明,在 TNFα 抑制治疗下,适应性免疫机制趋于正常化,这可能是炎症控制的结果,但有助于细胞因子阻断治疗的疗效。

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