Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India.
Department of Biochemistry, Panjab University, Chandigarh, India.
Clin Rheumatol. 2019 Jan;38(1):37-44. doi: 10.1007/s10067-018-4011-8. Epub 2018 Feb 20.
Rheumatoid arthritis is considered a T-lymphocyte-mediated disease. However, studies have focussed on CD4 T-lymphocytes, ignoring CD8 T-lymphocytes despite the latter being found abundantly in the synovium. Specifically, there is little data of the effect of methotrexate, the gold-standard DMARD, on various CD8 cytokine T-lymphocyte subsets and conflicting data on CD4 subsets. In this prospective study, patients with active rheumatoid arthritis, who were 18 to 65 years of age, were treated with methotrexate (up to 25 mg per week) for 24 weeks. At baseline and 24 weeks, frequencies of CD8IFNγ, CD8IL17, CD8IL4, corresponding CD4 subsets and plasma levels of IFNγ, IL-12, IL-10, IL-4 and IL-17 were determined by flow cytometry. These are summarised as median (IQR = interquartile range, 25th-75th percentile) and paired data compared using Wilcoxon signed rank test. This study included 67 patients (F/M = 4:1) with rheumatoid arthritis, 57 (85%) being RF positive and 20 receiving prednisolone at baseline. Mean (± SD) dose of methotrexate at 24 weeks was 22.9 ± 3.0 mg per week. On treatment with methotrexate, there was a significant (p = 0.04) decline in CD8IFNγ cells from 37.2 (IQR 19.4-60.2) to 22.7% (IQR 8.5-49.7) and a marginal increase in CD8IL17 cells from 0.3 (IQR 0.1-0.6) to 0.4 (IQR 0.2-1.2), p = 0.006. There was no significant change in the other subsets. There was also a significant decline in circulating levels of IL-12, IL-10 and IL-17 and marginal increase in IL-4. On evaluating by response, non-responders but not responders had a significant increase in CD8IL17 (p = 0.01). There is a significant decline of CD8IFNγ T cells and marginal increase in CD8IL17 T cells after methotrexate. Change in Tc1 subset may be mediated through reduction in IL-12 levels.
类风湿关节炎被认为是一种 T 淋巴细胞介导的疾病。然而，研究集中在 CD4 T 淋巴细胞上，尽管 CD8 T 淋巴细胞在滑膜中大量存在，但却忽略了它们。具体来说，关于甲氨蝶呤（治疗类风湿关节炎的金标准 DMARD 药物）对各种 CD8 细胞因子 T 淋巴细胞亚群的影响的数据很少，而关于 CD4 亚群的数据则相互矛盾。在这项前瞻性研究中，纳入了 18 至 65 岁的活动性类风湿关节炎患者，这些患者接受了为期 24 周的甲氨蝶呤（每周高达 25mg）治疗。在基线和 24 周时，通过流式细胞术确定了 CD8IFNγ、CD8IL17、CD8IL4、相应的 CD4 亚群以及 IFNγ、IL-12、IL-10、IL-4 和 IL-17 的血浆水平。这些数据总结为中位数（IQR=四分位间距，25%至 75%），并使用 Wilcoxon 符号秩检验比较配对数据。该研究纳入了 67 名（男女比例为 4:1）类风湿关节炎患者，其中 57 名（85%）类风湿因子阳性，20 名患者在基线时接受了泼尼松龙治疗。24 周时甲氨蝶呤的平均（± SD）剂量为 22.9±3.0mg/周。接受甲氨蝶呤治疗后，CD8IFNγ 细胞从 37.2%（IQR 19.4-60.2）降至 22.7%（IQR 8.5-49.7），具有显著统计学意义（p=0.04），而 CD8IL17 细胞从 0.3%（IQR 0.1-0.6）增至 0.4%（IQR 0.2-1.2），具有边缘统计学意义（p=0.006）。其他亚群没有显著变化。循环 IL-12、IL-10 和 IL-17 水平也显著下降，IL-4 水平略有增加。通过评估反应，无应答者而非应答者的 CD8IL17 水平显著升高（p=0.01）。甲氨蝶呤治疗后，CD8IFNγ T 细胞显著减少，CD8IL17 T 细胞略有增加。Tc1 亚群的变化可能是通过降低 IL-12 水平介导的。
