Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo; and Department of Internal Medicine, Tokyo Dental College Ichikawa General Hospital, Chiba, Japan.
Clin Exp Rheumatol. 2018 Jul-Aug;36(4):540-544. Epub 2018 Jan 31.
Although circulating CD14brightCD16+ monocyte subsets are increased in inflammatory disease, the pathogenesis of the increase in the inflammatory condition of the cells is still unclear and the relationship to cytokines is unknown particularly in rheumatoid arthritis (RA). The purpose of this study was to investigate the influence anti-cytokine treatment has on CD14brightCD16+ monocytes in patients with RA.
Thirty-two RA patients and 14 healthy volunteers (HV) were enrolled in this study. All the patients had never been treated with methotrexate (MTX) or biological agents. Peripheral blood samples and clinical information of the patients were obtained at the time of 0, 12 and 24 weeks of treatment. Peripheral blood samples were also obtained from the HV. The expression levels of CD14 and CD16 on monocytes were measured by flow cytometry (FCM).
Eight patients received anti-interleukin (IL)-6 receptor antibody, tocilizumab (TCZ) treatment alone, 12 patients received anti-tumour necrosis factor (TNF)-α antibody, adalimumab (ADA) with MTX treatment and the others received only MTX treatment. FCM analysis revealed that the proportion of CD14brightCD16+ monocytes significantly increased in patients at baseline compared with HV. The proportion of CD14brightCD16+ monocytes significantly decreased after TCZ, and ADA with MTX treatment. The proportion of intermediate monocytes was significantly and positively correlated with disease activity and it improved in accordance with the proportion of CD14brightCD16+ monocytes after inhibition of signal transduction of inflammatory cytokines.
We showed that the population of CD14brightCD16+ monocytes significantly decreased with the change of disease activity by key cytokines, IL-6 or TNF-α signal blockade in RA. This result indicates that the proportion of those monocytes is important for reflecting disease activity in RA.
虽然循环 CD14brightCD16+单核细胞亚群在炎症性疾病中增加，但这些细胞炎症状态增加的发病机制仍不清楚，与细胞因子的关系也不清楚，尤其是在类风湿关节炎（RA）中。本研究旨在探讨抗细胞因子治疗对 RA 患者 CD14brightCD16+单核细胞的影响。
本研究纳入了 32 例 RA 患者和 14 名健康志愿者（HV）。所有患者均从未接受过甲氨蝶呤（MTX）或生物制剂治疗。在治疗的 0、12 和 24 周时，采集患者的外周血样本和临床资料。同时从 HV 中采集外周血样本。采用流式细胞术（FCM）检测单核细胞上 CD14 和 CD16 的表达水平。
8 例患者接受抗白细胞介素（IL）-6 受体抗体托珠单抗（TCZ）单独治疗，12 例患者接受抗肿瘤坏死因子（TNF）-α 抗体阿达木单抗（ADA）联合 MTX 治疗，其余患者仅接受 MTX 治疗。FCM 分析显示，与 HV 相比，基线时患者 CD14brightCD16+单核细胞的比例显著增加。TCZ 和 ADA 联合 MTX 治疗后，CD14brightCD16+单核细胞的比例显著降低。中间单核细胞的比例与疾病活动度呈显著正相关，并且随着炎症细胞因子信号转导的抑制，其与 CD14brightCD16+单核细胞的比例一起改善。
我们表明，在 RA 中，通过关键细胞因子（IL-6 或 TNF-α）信号阻断，CD14brightCD16+单核细胞的数量随着疾病活动度的变化而显著减少。这一结果表明，这些单核细胞的比例对于反映 RA 中的疾病活动度很重要。
