Unexpected arterial wall and cellular inflammation in patients with rheumatoid arthritis in remission using biological therapy: a cross-sectional study.
Unexpected arterial wall and cellular inflammation in patients with rheumatoid arthritis in remission using biological therapy: a cross-sectional study.
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DOI：
10.1186/s13075-016-1008-z
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发表时间：
2016-05-21
影响因子：
4.9
通讯作者：
Stroes ES
中科院分区：
文献类型：
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作者：
Bernelot Moens SJ;van der Valk FM;Strang AC;Kroon J;Smits LP;Kneepkens EL;Verberne HJ;van Buul JD;Nurmohamed MT;Stroes ES
越来越多的类风湿性关节炎(RA)患者(高达40%)获得缓解，但这是否也能使他们的心血管风险正常化仍有待阐明。使用肿瘤坏死因子抑制剂的短期治疗可以降低动脉壁炎症，但不能达到健康对照组的水平。我们调查了长期缓解期的RA患者是否以动脉壁炎症活动正常化为特征，以及这是否依赖于使用的药物类型(肿瘤坏死因子抑制剂与非生物疾病修改的抗风湿药物(DMARD))。用18F-脱氧葡萄糖(18F-FDG)正电子发射断层扫描/计算机断层扫描(PET/CT)对缓解期RA患者(疾病活动评分(DAS28)和6个月(Lt；2.6))和健康对照组的动脉壁炎症、骨髓和脾活动(祖细胞活性指数)进行了评价。我们用流式细胞术和内皮迁移实验进行了单核细胞的体外鉴定。总体而言，长期缓解期RA患者(n = 23例)和对照组(n = 17例)动脉壁炎症情况相似。然而，目前使用抗肿瘤坏死因子治疗的RA患者(n = 13，疾病活动性评分1.98[1.8-2.2])的动脉壁18F- = 摄取量几乎是使用DMARD(但之前使用抗肿瘤坏死因子治疗)的患者的1.2倍(n ARDS 10，疾病活动性评分2.24[1.3-2.5])，在多元线性回归分析中，这似乎主要是由于他们的风湿病持续时间较长所致。这与单核细胞表面前黏附分子(CCR2)和迁移分子(CD11c，CD18)的表达增加以及随之而来的迁移能力的增强相一致。最后，我们发现，与DMARDS患者和对照组相比，使用抗肿瘤坏死因子治疗的RA患者的骨髓和脾中的活性增加。尽管使用了有效的肿瘤坏死因子阻断疗法，仍有一部分临床缓解的类风湿关节炎患者激活了单核细胞，并增加了动脉壁的炎症。在这些受试者中，RA病程是影响动脉壁炎症水平的最重要因素。这种炎症状态的增加意味着这些患者的心血管风险更高，因此他们可能需要更严格的心血管风险管理。本文的在线版本(doi：10.1186/s13075-0161008-z)包含补充材料，授权用户可以使用。
Increasing numbers of patients (up to 40 %) with rheumatoid arthritis (RA) achieve remission, yet it remains to be elucidated whether this also normalizes their cardiovascular risk. Short-term treatment with TNF inhibitors lowers arterial wall inflammation, but not to levels of healthy controls. We investigated whether RA patients in long-term remission are characterized by normalized inflammatory activity of the arterial wall and if this is dependent on type of medication used (TNF-inhibitor versus nonbiological disease-modifying antirheumatic drugs (DMARDs)). Arterial wall inflammation, bone marrow and splenic activity (index of progenitor cell activity) was assessed with 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in RA patients in remission (disease activity score (DAS28) <2.6 for >6 months) and healthy controls. We performed ex vivo characterization of monocytes using flow cytometry and a transendothelial migration assay. Overall, arterial wall inflammation was comparable in RA patients (n = 23) in long-term remission and controls (n = 17). However, RA subjects using current anti-TNF therapy (n = 13, disease activity score 1.98[1.8–2.2]) have an almost 1.2-fold higher 18F-FDG uptake in the arterial wall compared to those using DMARDs (but with previous anti-TNF therapy) (n = 10, disease activity score 2.24[1.3–2.5]), which seemed to be predominantly explained by longer duration of their rheumatic disease in a multivariate linear regression analysis. This coincided with increased expression of pro-adhesive (CCR2) and migratory (CD11c, CD18) surface markers on monocytes and a concomitant increased migratory capacity. Finally, we found increased activity in bone marrow and spleen in RA patients using anti-TNF therapy compared to those with DMARDs and controls. A subset of patients with RA in clinical remission have activated monocytes and increased inflammation in the arterial wall, despite the use of potent TNF blocking therapies. In these subjects, RA disease duration was the most important contributor to the level of arterial wall inflammation. This increased inflammatory state implies higher cardiovascular risk in these patients, who thus may require more stringent CV risk management. The online version of this article (doi:10.1186/s13075-016-1008-z) contains supplementary material, which is available to authorized users.