Alterations in peripheral blood memory B cells in patients with active rheumatoid arthritis are dependent on the action of tumour necrosis factor.
Alterations in peripheral blood memory B cells in patients with active rheumatoid arthritis are dependent on the action of tumour necrosis factor.
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DOI：
10.1186/ar2718
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发表时间：
2009
影响因子：
4.9
通讯作者：
Lipsky PE
中科院分区：
文献类型：
--
作者：
Souto-Carneiro MM;Mahadevan V;Takada K;Fritsch-Stork R;Nanki T;Brown M;Fleisher TA;Wilson M;Goldbach-Mansky R;Lipsky PE
在各种自身免疫性疾病中已经观察到外周血记忆B细胞亚群的紊乱，但在类风湿关节炎(RA)中尚未完全被描述。此外，肿瘤坏死因子在调节类风湿关节炎患者外周血记忆B细胞亚群变化中的可能作用尚不清楚。本文分析了活动期类风湿关节炎患者外周血和滑膜中B细胞亚群的频率和分布。此外，在使用特定的肿瘤坏死因子中和抗体英夫利昔单抗的临床试验中，评估了肿瘤坏死因子在导致类风湿关节炎患者记忆B细胞亚群紊乱中的可能作用。RA患者外周血中IGD+CD27+记忆B细胞的比例显著低于正常人，而切换后IGD-CD27+细胞随着病程的延长而积聚。值得注意的是，转换前的IGD+CD27+和转换后的IGD-CD27+记忆B细胞都聚集在RA患者的滑膜中。最后，抗肿瘤坏死因子治疗增加了外周血中IGD+CD27记忆B细胞的转换前频率。这些数据表明，RA患者外周血中IGD+CD27+切换前记忆B细胞的减少反映了它们在滑膜组织中的积聚。此外，在用英夫利昔单抗特异性阻断肿瘤坏死因子的患者中，外周血切换前记忆B细胞显著增加，这表明类风湿关节炎患者的记忆B细胞向炎症组织的运输受肿瘤坏死因子的调节，并可通过中和肿瘤坏死因子来纠正。
Disturbances in peripheral blood memory B cell subpopulations have been observed in various autoimmune diseases, but have not been fully delineated in rheumatoid arthritis (RA). Additionally, the possible role of tumour necrosis factor (TNF) in regulating changes in specific peripheral blood memory B cell subsets in RA is still unclear. The frequency and distribution of B cell subsets in the peripheral blood and synovial membrane of active RA patients with long-standing disease have been analysed. Additionally, the possible role of TNF in causing disturbances in memory B cell subsets in RA patients was assessed in a clinical trial with the specific TNF-neutralising antibody, infliximab. RA patients, independent of disease duration, have a significantly lower frequency of peripheral blood pre-switch IgD+CD27+ memory B cells than healthy individuals, whereas post-switch IgD-CD27+ accumulate with increased disease duration. Notably, both pre-switch IgD+CD27+ and post-switch IgD-CD27+ memory B cells accumulate in the synovial membrane of RA patients. Finally, anti-TNF therapy increased the frequency of pre-switch IgD+CD27 memory B cells in the peripheral blood. The data suggest that decreases in peripheral blood IgD+CD27+ pre-switch memory B cells in RA reflect their accumulation in the synovial tissue. Moreover, the significant increase in the peripheral blood pre-switch memory B cells in patients who underwent specific TNF-blockade with infliximab indicates that trafficking of memory B cells into inflamed tissue in RA patients is regulated by TNF and can be corrected by neutralising TNF.