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肿瘤坏死因子抑制剂联合甲氨蝶呤诱导的缓解与类风湿关节炎患者外周初始B细胞的变化相关。

Remission Induced by TNF Inhibitors Plus Methotrexate is Associated With Changes in Peripheral Naïve B Cells in Patients With Rheumatoid Arthritis.

作者信息

Hernández-Breijo Borja, Plasencia-Rodríguez Chamaida, Navarro-Compán Victoria, García-Hoz Carlota, Nieto-Gañán Israel, Sobrino Cristina, Bachiller-Corral Javier, Díaz-Almirón Mariana, Martínez-Feito Ana, Jurado Teresa, Lapuente-Suanzes Paloma, Bonilla Gema, Pijoán-Moratalla Cristina, Roy Garbiñe, Vázquez-Díaz Mónica, Balsa Alejandro, Villar Luisa M, Pascual-Salcedo Dora, Rodríguez-Martín Eulalia

机构信息

Immuno-Rheumatology Research Group, Hospital La Paz Institute for Health Research-IdiPAZ, Madrid, Spain.

Rheumatology, La Paz University Hospital, Madrid, Spain.

出版信息

Front Med (Lausanne). 2021 Jun 17;8:683990. doi: 10.3389/fmed.2021.683990. eCollection 2021.

Abstract

Biological therapies, such as TNF inhibitors (TNFi), are increasing remission (REM) rates in rheumatoid arthritis (RA) patients, although these are still limited. The aim of our study was to analyze changes in the profile of peripheral blood mononuclear cells (PBMC) in patients with RA treated with TNFi in relation to the clinical response. This is a prospective and observational study including 78 RA patients starting the first TNFi. PBMC were analyzed by flow cytometry both at baseline and at 6 months. Disease activity at the same time points was assessed by DAS28, establishing DAS28 ≤ 2.6 as the criteria for REM. Logistic regression models were employed to analyze the association between the changes in PBMC and REM. After 6 months of TNFi treatment, 37% patients achieved REM by DAS28. Patients who achieved REM showed a reduction in the percentage of naive B cells, but only when patients had received concomitant methotrexate (MTX) (OR: 0.59; 95% CI: 0.39-0.91). However, no association was found for patients who did not receive concomitant MTX (OR: 0.85; 95% CI: 0.63-1.16). In conclusion, PBMC, mainly the B-cell subsets, are modified in RA patients with TNFi who achieve clinical REM. A significant decrease in naive B-cell percentage is associated with achieving REM after 6 months of TNFi treatment in patients who received concomitant therapy with MTX.

摘要

生物疗法,如肿瘤坏死因子抑制剂(TNFi),正在提高类风湿关节炎(RA)患者的缓解(REM)率,尽管目前这些缓解率仍然有限。我们研究的目的是分析接受TNFi治疗的RA患者外周血单个核细胞(PBMC)谱的变化与临床反应之间的关系。这是一项前瞻性观察性研究,纳入了78例开始接受首次TNFi治疗的RA患者。在基线和6个月时通过流式细胞术分析PBMC。在相同时间点通过DAS28评估疾病活动度,将DAS28≤2.6确立为缓解标准。采用逻辑回归模型分析PBMC变化与缓解之间的关联。TNFi治疗6个月后,37%的患者通过DAS28达到缓解。达到缓解的患者幼稚B细胞百分比降低,但仅在患者同时接受甲氨蝶呤(MTX)治疗时出现这种情况(比值比:0.59;95%置信区间:0.39 - 0.91)。然而,未接受MTX联合治疗的患者未发现此关联(比值比:0.85;95%置信区间:0.63 - 1.16)。总之,在通过TNFi治疗达到临床缓解的RA患者中,PBMC,主要是B细胞亚群发生了改变。在接受MTX联合治疗的患者中,TNFi治疗6个月后幼稚B细胞百分比显著降低与达到缓解相关。

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