High levels of natural killer cells are associated with response to tocilizumab in patients with severe rheumatoid arthritis
High levels of natural killer cells are associated with response to tocilizumab in patients with severe rheumatoid arthritis
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DOI：
10.1093/rheumatology/keu363
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发表时间：
2015-04-01
期刊：
影响因子：
5.5
通讯作者：
Morel, Jacques
中科院分区：
文献类型：
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作者：
Daien, Claire Immediato;Gailhac, Sarah;Morel, Jacques
目标.我们的目的是评估托珠单抗（TCZ），一种IL-6受体抑制剂，对RA患者的B，T，NK和NKT细胞的影响，并研究缓解的细胞类型预测因子。我们还比较了RA患者和对照组的NK细胞。纳入研究的RA患者符合2010年ACR/欧洲抗风湿联盟（EULAR）标准，正在接受稳定剂量的类固醇治疗，并且在前一年没有接受利妥昔单抗治疗。采用流式细胞仪检测不同B和T细胞亚群、NK细胞和NKT细胞，并沿着穿孔素A和颗粒酶B检测NK细胞的细胞毒性。我们纳入了92例RA患者，其中20例需要TCZ治疗，15例需要抗TNF药物，25例对照。基线时，CD 56（dim）CD 16（+）CD 3（-）NK细胞比例与28关节DAS（DAS 28）呈负相关。在接受TCZ治疗的患者中，CD 3（-）CD 56（+）NK细胞的基线比例与3个月时DAS 28的变化呈负相关，3个月时DAS 28缓解的患者的比例是其他患者的3倍。3个月时，CD 56（bri）CD 16（-）NK细胞比例的变化与DAS 28的变化呈线性相关。NK细胞的基线比例不能预测抗TNF治疗3个月后疾病活动度的变化。TCZ处理后NK细胞中穿孔素含量增加。这项研究支持NK细胞参与RA和TCZ的作用机制。如果结果得到证实，基线时的NK细胞可能是TCZ应答的预测因素。
Objectives. We aimed to assess the effect of tocilizumab (TCZ), an IL-6 receptor inhibitor, on B, T, NK and NKT cells in patients with RA and to study the cell type predictors of remission. We also compared NK cells in patients with RA and in controls.Methods. RA patients included in the study met the 2010 ACR/European League Against Rheumatism (EULAR) criteria, were receiving stable doses of steroids and had not received rituximab in the previous year. Different B and T cell subsets, NK cells and NKT cells were assessed by flow cytometry along with perforin A and granzyme B to estimate NK cell cytotoxicity.Results. We included 92 RA patients, including 20 requiring TCZ treatment and 15 requiring anti-TNF drugs, and 25 controls. At baseline, the proportion of CD56(dim)CD16(+)CD3(-) NK cells was inversely correlated with the 28-joint DAS (DAS28). In TCZ-treated patients, the baseline proportion of CD3(-)CD56(+) NK cells was inversely correlated with the change in DAS28 at 3 months and the proportion was 3-fold greater for patients with DAS28 remission at 3 months than other patients. Change in the proportion of CD56(bri)CD16(-) NK cells was linearly correlated with change in the DAS28 at 3 months. The baseline proportion of NK cells did not predict change in disease activity at 3 months with anti-TNF therapy. The perforin content in NK cells increased with TCZ treatment.Conclusion. This study supports NK cell involvement in RA and in the TCZ mechanism of action. NK cells at baseline could be a predictive factor of TCZ response if results are confirmed.