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骨关节炎性滑液和滑液生物标志物在评估膝关节关节内肿瘤坏死因子-α阻断中的作用。

Synovial effusion and synovial fluid biomarkers in psoriatic arthritis to assess intraarticular tumor necrosis factor-α blockade in the knee joint.

机构信息

Department of Clinical and Experimental Medicine, University of Padova, Padova, Italy.

出版信息

Arthritis Res Ther. 2010;12(4):R148. doi: 10.1186/ar3090. Epub 2010 Jul 19.

Abstract

INTRODUCTION

The purpose of this study was the evaluation of synovial effusion (SE), synovial fluid (SF) and synovial tissue (ST) biomarkers in relation to disease activity indexes to assess the response to intraarticular (IA) tumor necrosis factor (TNF)-α blockers in psoriatic arthritis (PsA).

METHODS

Systemic and local disease activity indexes (disease activity score (DAS); the Ritchie articular index (mRAI), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP); Thompson articular (THOMP) and joint articular (KJAI)-Index ) and ST samples were assessed at baseline, throughout treatment, and during the follow-up in 14 patients affected with PsA who underwent IA injections (0.5 ml to 12.5 mg) in the knee joint of etanercept (E) or placebo (P) once every two weeks for a 10-week period. Total SF white blood cell (WBC) counts (WBC/μl) and SF cytokine/chemokine (CK/CCK) levels were measured before IA-E at baseline, after IA-E, and as long as there were adequate amounts of SF for knee aspiration (post). Characterization of synovial mononuclear cell infiltration and synovial vessels was carried out in 8 out of 14 knees by staining serial sections of synovial tissue biopsies for CD45, CD3, CD68, CD31 and CD105.

RESULTS

At baseline, CRP and/or ESR were significantly correlated with SF-CK (interleukin- (IL-)1β, IL-1Ra, IL-6, IL-8) and CCK (CCL3). Post-IA injections, there was a decrease in SE in the knees in which aspiration following IA-E injection was possible as well as a significant reduction in SF WBC/μl and in SF-CK (IL-1β, IL-1Ra, IL-6 and IL-22). Pre- and post-IA-E injections, there were significant correlations between ST markers and SF-CK (IL-1β with CD45; IL-1β and IL-6 with CD31) and between SF-CCK (CCL4 and CCL3 with CD3). At the end of the study, there was a significant reduction in disease activity indexes (CRP, DAS, RAI, THOMP, KJAI) as well as in the ST markers (CD45; CD3).

CONCLUSIONS

Synovial effusion regression is a reliable indicator of the response to IA TNF-α blockers in PsA patients as it is confirmed by the correlation between SF biomarkers to disease activity and synovial tissue inflammation.

摘要

简介

本研究旨在评估滑液(SE)、滑液(SF)和滑膜组织(ST)生物标志物与疾病活动指标的关系,以评估在银屑病关节炎(PsA)患者中关节内(IA)肿瘤坏死因子(TNF)-α 阻滞剂的反应。

方法

在 14 名接受 IA 注射(0.5 毫升至 12.5 毫克)的 PsA 患者中,评估基线时、整个治疗期间和随访期间的全身和局部疾病活动指标(疾病活动评分(DAS);Ritchie 关节指数(mRAI)、红细胞沉降率(ESR)和 C 反应蛋白(CRP);Thompson 关节(THOMP)和关节关节(KJAI)-Index)和 ST 样本。在 IA-E 之前,在基线时、IA-E 后以及只要有足够数量的 SF 进行膝关节抽吸(post)时,测量 SF 白细胞总数(WBC/μl)和 SF 细胞因子/趋化因子(CK/CCK)水平。对 14 个膝关节中的 8 个进行滑膜单核细胞浸润和滑膜血管的特征描述,对滑膜组织活检的连续切片进行 CD45、CD3、CD68、CD31 和 CD105 染色。

结果

在基线时,CRP 和/或 ESR 与 SF-CK(白细胞介素(IL)-1β、IL-1Ra、IL-6、IL-8)和 CCK(CCL3)显著相关。IA 注射后,在可行 IA-E 注射后抽吸的膝关节中,SE 减少,SF WBC/μl 和 SF-CK(IL-1β、IL-1Ra、IL-6 和 IL-22)显著降低。IA-E 注射前后,ST 标志物与 SF-CK(IL-1β 与 CD45;IL-1β 和 IL-6 与 CD31)之间以及 SF-CCK(CCL4 和 CCL3 与 CD3)之间存在显著相关性。研究结束时,疾病活动指标(CRP、DAS、RAI、THOMP、KJAI)以及 ST 标志物(CD45;CD3)显著降低。

结论

滑液消退是银屑病关节炎患者对 IA TNF-α 阻滞剂反应的可靠指标,因为 SF 生物标志物与疾病活动和滑膜组织炎症之间的相关性得到了证实。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b60/2945042/fde7c93d59ee/ar3090-1.jpg

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