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利妥昔单抗诱导类风湿关节炎患者T细胞耗竭:与临床反应的关联

Rituximab-induced T cell depletion in patients with rheumatoid arthritis: association with clinical response.

作者信息

Mélet J, Mulleman D, Goupille P, Ribourtout B, Watier H, Thibault G

机构信息

Université François-Rabelais de Tours, CNRS, UMR 7292, and Centre Hospitalier Régional Universitaire de Tours, Tours, France.

出版信息

Arthritis Rheum. 2013 Nov;65(11):2783-90. doi: 10.1002/art.38107.

Abstract

OBJECTIVE

Rituximab, a monoclonal antibody specifically targeting CD20, induces B cell depletion and is effective in the treatment of rheumatoid arthritis (RA). This study was undertaken to evaluate whether routine monitoring of lymphocyte subpopulations, especially T cells, may be useful in patients receiving rituximab for RA.

METHODS

We examined data on all RA patients receiving rituximab between July 2007 and November 2012 in our center. Peripheral blood CD3+, CD4+, CD8+, CD3-CD56+, and CD19+ lymphocyte counts before and during the first course of rituximab were measured by flow cytometry. The Mann-Whitney nonparametric test was used to compare lymphocyte subpopulation counts before and during treatment.

RESULTS

Data on 52 patients were examined. Rituximab induced unexpected and substantial depletion of T cells, mainly CD4+ cells, in most patients. The CD4+ cell count decreased by a mean ± SD of 37 ± 33% as compared to baseline at week 12, reaching <200 cells/μl in 3 patients. Importantly, lack of CD4+ cell depletion was associated with no clinical response. Therefore, the mechanism of action of rituximab may depend at least in part on T cells.

CONCLUSION

Rituximab induces substantial T cell depletion, mainly of CD4+ cells, which is associated with the clinical response in RA. Routine monitoring of T cells may be useful in the clinical setting of RA.

摘要

目的

利妥昔单抗是一种特异性靶向CD20的单克隆抗体,可诱导B细胞耗竭,对类风湿关节炎(RA)的治疗有效。本研究旨在评估对接受利妥昔单抗治疗RA的患者进行淋巴细胞亚群,尤其是T细胞的常规监测是否有用。

方法

我们检查了2007年7月至2012年11月期间在本中心接受利妥昔单抗治疗的所有RA患者的数据。通过流式细胞术测量利妥昔单抗第一个疗程之前及期间外周血CD3 +、CD4 +、CD8 +、CD3 - CD56 +和CD19 +淋巴细胞计数。采用曼 - 惠特尼非参数检验比较治疗前和治疗期间淋巴细胞亚群计数。

结果

检查了52例患者的数据。在大多数患者中,利妥昔单抗诱导了意外且显著的T细胞耗竭,主要是CD4 +细胞。与第12周时的基线相比,CD4 +细胞计数平均下降了37±33%,3例患者的CD4 +细胞计数降至<200个细胞/μl。重要的是,缺乏CD4 +细胞耗竭与无临床反应相关。因此,利妥昔单抗的作用机制可能至少部分取决于T细胞。

结论

利妥昔单抗诱导显著的T细胞耗竭,主要是CD4 +细胞,这与RA的临床反应相关。对T细胞进行常规监测在RA的临床环境中可能有用。

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