早期银屑病关节炎和类风湿关节炎患者中IL-17A、Dkk1和TGF-β1的滑膜免疫组化反应性较高可预测生物制剂的使用。

Higher Synovial Immunohistochemistry Reactivity of IL-17A, Dkk1, and TGF-β1 in Patients with Early Psoriatic Arthritis and Rheumatoid Arthritis Could Predict the Use of Biologics.

作者信息

Pinto-Tasende Jose A, Fernandez-Moreno Mercedes, Rego Perez Ignacio, Fernandez-Lopez J Carlos, Oreiro-Villar Natividad, De Toro Santos F Javier, Blanco-García Francisco J

机构信息

Department of Rheumatology, Institute of Biomedical Research of A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña, Universidade de A Coruña, 15006 A Coruña, Spain.

Institute of Biomedical Research of A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña, 15006 A Coruña, Spain.

出版信息

Biomedicines. 2024 Apr 8;12(4):815. doi: 10.3390/biomedicines12040815.

DOI:10.3390/biomedicines12040815

PMID:38672170

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11048598/

Abstract

BACKGROUND

Delay in diagnosis and therapy in patients with arthritis commonly leads to progressive articular damage. The study aimed to investigate the immunohistochemical reactivity of synovial cytokines associated with inflammation and the bone erosives/neoformatives processes among individuals diagnosed with psoriatic arthritis (PsA), rheumatoid arthritis (RA), osteoarthritis (OA), and radiographic axial spondyloarthritis (r-axSpA), with the intention of identifying potential biomarkers.

METHODS

Specimens were collected from the inflamed knee joints of patients referred for arthroscopic procedures, and the synovial tissue (ST) was prepared for quantifying protein expression through immunohistochemical analysis (% expressed in Ratio_Area-Intensity) for TGF-β1, IL-17A, Dkk1, BMP2, BMP4, and Wnt5b. The collected data underwent thorough analysis and examination of their predictive capabilities utilising receiver operating characteristic (ROC) curves.

RESULTS

Valid synovial tissue samples were acquired from 40 patients for IHC quantification analysis. Initially, these patients had not undergone treatment with biologics. However, after 5 years, 4 out of 13 patients diagnosed with PsA and two out of nine patients diagnosed with RA had commenced biologic treatments. Individuals with early PsA who received subsequent biologic treatment exhibited significantly elevated IHC reactivity in ST for TGF-β1 ( = 0.015). Additionally, patients with both PsA and RA who underwent biologic therapy displayed increased IHC reactivity for IL-17A ( = 0.016), TGF-β1 ( = 0.009), and Dkk1 ( = 0.042). ROC curve analysis of IHC reactivity for TGF-β1, Dkk1, and IL-17A in the synovial seems to predict future treatment with biologics in the next 5 years with the area under the curve (AUC) of a combined sum of the three values: AUC: 0.828 (95% CI: 0.689-0.968; 0.005) S 75% E 84.4%.

CONCLUSIONS

Higher synovial immunohistochemistry reactivity of IL-17A, Dkk1, and TGF-β1 in patients with early psoriatic arthritis and rheumatoid arthritis may serve as potential indicators for predicting the necessity of utilising biologic treatments.

摘要

背景

关节炎患者诊断和治疗的延迟通常会导致进行性关节损伤。本研究旨在调查诊断为银屑病关节炎（PsA）、类风湿关节炎（RA）、骨关节炎（OA）和放射学轴向脊柱关节炎（r-axSpA）的个体中与炎症以及骨侵蚀/新骨形成过程相关的滑膜细胞因子的免疫组化反应性，以确定潜在的生物标志物。

方法

从因关节镜手术转诊的患者发炎膝关节收集标本，并制备滑膜组织（ST），通过免疫组化分析（以Ratio_Area-Intensity表示的百分比）对TGF-β1、IL-17A、Dkk1、BMP2、BMP4和Wnt5b进行蛋白表达定量。利用受试者工作特征（ROC）曲线对收集的数据进行全面分析并检验其预测能力。

结果

从40例患者中获取了有效的滑膜组织样本用于免疫组化定量分析。最初，这些患者未接受生物制剂治疗。然而，5年后，13例诊断为PsA的患者中有4例以及9例诊断为RA的患者中有2例开始接受生物治疗。接受后续生物治疗的早期PsA患者滑膜中TGF-β1的免疫组化反应性显著升高（P = 0.015）。此外，接受生物治疗的PsA和RA患者IL-17A（P = 0.016）、TGF-β1（P = 0.009）和Dkk1（P = 0.042）的免疫组化反应性增加。滑膜中TGF-β1、Dkk1和IL-17A免疫组化反应性的ROC曲线分析似乎可预测未来5年内生物制剂治疗情况，三者合并值的曲线下面积（AUC）为：AUC：0.828（95%CI：0.689 - 0.968；P = 0.005），敏感度75%，特异度84.4%。