Increase of peripheral CXCR3 positive T lymphocytes upon treatment of RA patients with TNF-α inhibitors
Increase of peripheral CXCR3 positive T lymphocytes upon treatment of RA patients with TNF-α inhibitors
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DOI：
10.1093/rheumatology/keh437
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发表时间：
2005-02-01
期刊：
影响因子：
5.5
通讯作者：
Villiger, PM
中科院分区：
文献类型：
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作者：
Aeberli, D;Seitz, M;Villiger, PM
Objective.探讨肿瘤坏死因子α（TNF-α）前体治疗类风湿关节炎（RA）患者淋巴细胞转运相关因子的调节作用。我们在TNF-α抑制剂（7例依那西普，7例英夫利西单抗）治疗前和治疗期间根据ACR标准检查了14例连续RA患者，并使用疾病活动评分（DAS-28）确定疾病活动。在治疗前、治疗6周和14周后分离外周血单个核细胞，并立即使用四色流式细胞术分析CD 3、CD 4和CD 8、趋化因子受体CXCR 3和CCR 4的表达、CD 45 RO表型以及干扰素γ（IFN-γ）和白细胞介素4（IL-4）的表达。我们发现在6周和14周后表达CXCR 3的CD 4和CD 8 T淋巴细胞显著增加。表达CCR 4的T淋巴细胞的总体比例似乎没有变化。超过一半的外周CD 4 T淋巴细胞显示记忆表型（CD 45 RO），在TNF-α抑制下无显著增加。活化后，高达30%的CXCR 3（+）/CD 4 T细胞表达IFN-γ，而表达IL-4的细胞很少。CXCR 3（+）/CD 4 T淋巴细胞与DAS-28呈显著负相关。用英夫利西单抗和依那西普抑制TNF-α导致RA患者外周血中CXCR 3阳性T淋巴细胞的持续蓄积。这表明在TNF-α抑制期间改变了淋巴细胞运输。
Objective. To explore the regulation of factors involved in lymphocyte trafficking in patients with rheumatoid arthritis (RA) undergoing treatment with tumour necrosis factor alpha (TNF-alpha) inhibitors.Methods. We examined 14 consecutive patients with RA according to ACR criteria prior to and during treatment with TNF-alpha inhibitors (seven etanercept, seven infliximab) and determined disease activity using the Disease Activity Score (DAS-28). Peripheral blood mononuclear cells were isolated before and after 6 and 14 weeks of treatment and analysed immediately for CD3, CD4 and CD8, expression of chemokine receptors CXCR3 and CCR4, CD45RO phenotype and for expression of interferon gamma (IFN-gamma) and interleukin 4 (IL-4) using four-colour flow cytometry.Results. We found significant increases in CD4 and CD8 T lymphocytes expressing CXCR3 after 6 and 14 weeks. The overall proportion of T lymphocytes expressing CCR4 appeared unchanged. More than half of peripheral CD4 T lymphocytes showed a memory phenotype (CD45RO), with a non-significant increase under TNF-alpha inhibition. Upon activation, up to 30% of CXCR3(+)/CD4 T cells expressed IFN-gamma, while IL-4-expressing cells were rare. There was a robust negative correlation between CXCR3(+)/CD4 T lymphocytes and DAS-28.Conclusions. TNF-alpha inhibition with infliximab and etanercept results in sustained accumulation of CXCR3 positive T lymphocytes in the peripheral blood of RA patients. This suggests altered lymphocyte trafficking during TNF-alpha inhibition.