The Parker Institute, Department of Rheumatology, Copenhagen University Hospital, Bispebjerg and Frederiksberg, Copenhagen, Denmark.
Translational Immunology, Biopharmaceutical Research Unit, Måløv, Novo Nordisk, Denmark.
PLoS One. 2018 May 22;13(5):e0197001. doi: 10.1371/journal.pone.0197001. eCollection 2018.
The need for biomarkers which can predict disease course and treatment response in rheumatoid arthritis (RA) is evident. We explored whether clinical and imaging responses to biologic disease modifying anti-rheumatic drug treatment (bDMARD) were associated with the individual's mediator production in explants obtained at baseline.
RA Patients were evaluated by disease activity score 28 joint C-reactive protein (DAS 28-)), colour Doppler ultrasound (CDUS) and 3 Tesla RA magnetic resonance imaging scores (RAMRIS). Explants were established from synovectomies from a needle arthroscopic procedure prior to initiation of bDMARD. Explants were incubated with the bDMARD in question, and the productions of interleukin-6 (IL-6), monocyte chemo-attractive protein-1 (MCP-1) and macrophage inflammatory protein-1-beta (MIP-1b) were measured by multiplex immunoassays. The changes in clinical and imaging variables following a minimum of 3 months bDMARD treatment were compared to the baseline explant results. Mixed models and Spearman's rank correlations were performed. P-values below 0.05 were considered statistically significant.
16 patients were included. IL-6 production in bDMARD-treated explants was significantly higher among clinical non-responders compared to responders (P = 0.04), and a lack of suppression of IL-6 by the bDMARDS correlated to a high DAS-28 (ρ = 0.57, P = 0.03), CDUS (ρ = 0.53, P = 0.04) and bone marrow oedema (ρ = 0.56, P = 0.03) at follow-up. No clinical association was found with explant MCP-1 production. MIP-1b could not be assessed due to a large number of samples below the detection limit.
Synovial explants appear to deliver a disease-relevant output testing which when carried out in advance of bDMARD treatment can potentially pave the road for a more patient tailored treatment approach with better treatment effects.
在类风湿关节炎（RA）中，需要能够预测疾病进程和治疗反应的生物标志物是显而易见的。我们探讨了生物改善抗风湿药物治疗（bDMARD）的临床和影像学反应是否与基线时获得的外植体中个体介质的产生有关。
通过疾病活动评分 28 关节 C 反应蛋白（DAS 28-）、彩色多普勒超声（CDUS）和 3 特斯拉 RA 磁共振成像评分（RAMRIS）对 RA 患者进行评估。外植体是通过在开始使用 bDMARD 之前进行的经皮关节镜下滑膜切除术获得的。用所研究的 bDMARD 孵育外植体，通过多重免疫测定法测量白细胞介素-6（IL-6）、单核细胞趋化蛋白-1（MCP-1）和巨噬细胞炎症蛋白-1-β（MIP-1b）的产生。将 bDMARD 治疗至少 3 个月后的临床和影像学变量的变化与基线外植体结果进行比较。进行混合模型和斯皮尔曼秩相关分析。P 值低于 0.05 被认为具有统计学意义。
共纳入 16 例患者。与反应者相比，临床无反应者 bDMARD 处理外植体中的 IL-6 产生显著更高（P = 0.04），并且 bDMARD 对 IL-6 的抑制缺乏与高 DAS-28（ρ = 0.57，P = 0.03）、CDUS（ρ = 0.53，P = 0.04）和骨髓水肿（ρ = 0.56，P = 0.03）相关。在外植体 MCP-1 产生方面未发现临床相关性。由于大量样本低于检测限，因此无法评估 MIP-1b。
滑膜外植体似乎提供了一种与疾病相关的检测结果，当在 bDMARD 治疗之前进行时，它可能为更个体化的治疗方法铺平道路，从而获得更好的治疗效果。
