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循环 IFN-γ 产生的 CD4+T 细胞和 IL-17A 产生的 CD4+T 细胞、HLA 共享表位和 ACPA 可能是类风湿关节炎患者对治疗反应的临床特征。

Circulating IFN-γ producing CD4+ T cells and IL-17A producing CD4+ T cells, HLA-shared epitope and ACPA may characterize the clinical response to therapy in rheumatoid arthritis patients.

机构信息

Department of Immunology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.

Department of Internal Diseases Medicine, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.

出版信息

Hum Immunol. 2020 May;81(5):228-236. doi: 10.1016/j.humimm.2020.02.008. Epub 2020 Feb 24.

Abstract

This study analyzed the association between peripheral distributions of helper T cell subsets, HLA shared-epitope (SE), anti-cyclic citrullinated peptide antibody (ACPA) and clinical response to therapy in rheumatoid arthritis (RA) patients. Frequencies of IFN-γ-producing CD4+T (Th1) and IL-17A-producing CD4+T (Th17) cells were determined by flow cytometry in 167 patients (114 cases with good-response (GR) and 53 poor-response (PR) based on DAS28). HLA-DRB1 alleles for patients and 150 healthy controls were determined by PCR-SSP. We observed that 65.2% of RA patients were SE, 63.4%ACPA, 43.7%SEACPA and 14.9% were SEACPA. Higher significantly proportions of Th1 and Th17 cells were found in RA patients than controls (P < 0.05) as well as in the SE or ACPARA patients compared to SE and ACPA patients. Increased frequencies of both Th subsets were found in SEACPA versus SEACPA patients (P < 0.001) and in the PR versus GR group (P < 0.001). We showed significant differences for Th cells frequencies between SE and SE patients in both groups, and between ACPA and ACPA cases in the PR group. Our findings suggest a close link between Th1 and Th17 cells proportions and HLA-SE/ACPA in the RA patients and remarkably in the PR group which could be indicative for the importance of immune monitoring for evaluation of response to therapy.

摘要

本研究分析了辅助性 T 细胞亚群外周分布、人类白细胞抗原共享表位(SE)、抗环瓜氨酸肽抗体(ACPA)与类风湿关节炎(RA)患者治疗反应之间的关系。通过流式细胞术测定了 167 例患者(根据 DAS28,114 例为良好反应(GR),53 例为不良反应(PR))中 IFN-γ 产生的 CD4+T(Th1)和 IL-17A 产生的 CD4+T(Th17)细胞的频率。采用 PCR-SSP 法测定患者和 150 例健康对照者的 HLA-DRB1 等位基因。我们发现,65.2%的 RA 患者为 SE,63.4%ACPA,43.7%SEACPA,14.9%为 SEACPA。与对照组相比(P<0.05),以及与 SE 或 ACPA 患者相比(P<0.05),RA 患者 Th1 和 Th17 细胞的比例明显更高。在 SEACPA 患者中,与 SEACPA 患者相比(P<0.001)和 PR 组相比(GR 组)(P<0.001),两种 Th 细胞亚群的频率均升高。在两组中,SE 和 SE 患者之间以及 PR 组中 ACPA 和 ACPA 病例之间的 Th 细胞频率存在显著差异。我们的研究结果表明,Th1 和 Th17 细胞比例与 RA 患者的 HLA-SE/ACPA 之间存在密切联系,在 PR 组中尤为明显,这可能表明免疫监测对于评估治疗反应的重要性。

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