Brighton and Sussex Medical School, University of Sussex, Brighton, UK.
Rheumatology (Oxford). 2020 Nov 1;59(11):3533-3539. doi: 10.1093/rheumatology/keaa220.
RA is an autoimmune inflammatory joint disease. Both RF and ACPA are associated with more progressive disease and higher levels of systemic inflammation. Monocyte activation of toll-like receptors (TLRs) by endogenous ligands is a potential source of increased production of systemic cytokines. RA monocytes have elevated TLRs, some of which are associated with the disease activity score using 28 joints (DAS28). The aim of this study was to measure TLR-induced cytokine production from monocytes, stratified by autoantibody status, to assess if their capacity to induce cytokines is related to autoantibody status or DAS28.
Peripheral blood monocytes isolated from RA patients and healthy controls were stimulated with TLR1/2, TLR2/6, TLR4, TLR5, TLR7, TLR8 and TLR9 ligands for 18 h before measuring IL-6, TNFα and IL-10. Serum was used to confirm the autoantibody status. Cytokine levels were compared with RF, ACPA and DAS28.
RA monocytes demonstrated significantly increased IL-6 and TNFα upon TLR1/2 stimulation and IL-6 and IL-10 upon TLR5 activation. TLR7 and TLR9 activation did not induce cytokines and no significant differences were observed between RA and healthy control monocytes upon TLR2/6, TLR4 or TLR8 activation. When stratified by ACPA or RF status there were no correlations between autoantibody status and elevated cytokine levels. However, TLR1/2-induced IL-6 did correlate with DAS28.
Elevated TLR-induced cytokines in RA monocytes were not related to ACPA or RF status. However, TLR1/2-induced IL-6 was associated with disease activity.
类风湿关节炎（RA）是一种自身免疫性炎症性关节疾病。类风湿因子（RF）和抗环瓜氨酸肽抗体（ACPA）均与疾病的进展和全身性炎症水平升高有关。内源性配体激活单核细胞的 Toll 样受体（TLR）是全身性细胞因子产生增加的潜在来源。RA 患者的单核细胞 TLR 表达上调，其中一些与 28 个关节疾病活动评分（DAS28）相关。本研究旨在通过测量 TLR 诱导的单核细胞产生细胞因子的情况，分析其是否与自身抗体状态或 DAS28 有关。
从 RA 患者和健康对照者的外周血中分离单核细胞，用 TLR1/2、TLR2/6、TLR4、TLR5、TLR7、TLR8 和 TLR9 配体刺激 18 小时后，测量白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）和白细胞介素-10（IL-10）的水平。采用血清学方法确定自身抗体状态。比较细胞因子水平与 RF、ACPA 和 DAS28 的相关性。
与健康对照组相比，RA 患者的单核细胞在 TLR1/2 刺激下可显著增加 IL-6 和 TNF-α的产生，在 TLR5 刺激下可显著增加 IL-6 和 IL-10 的产生。TLR7 和 TLR9 激活后不能诱导细胞因子产生，且 TLR2/6、TLR4 或 TLR8 激活后，RA 患者与健康对照组单核细胞之间也未观察到明显差异。当根据 ACPA 或 RF 状态进行分层时，自身抗体状态与细胞因子水平升高之间没有相关性。然而，TLR1/2 诱导的 IL-6 与 DAS28 呈正相关。
RA 患者单核细胞中 TLR 诱导的细胞因子升高与 ACPA 或 RF 状态无关。然而，TLR1/2 诱导的 IL-6 与疾病活动度相关。
