Ex vivo cell-based assay for assessment of response to TNF inhibitors in patients with rheumatic diseases.

IF 4.7 2区医学 Q1 RHEUMATOLOGY

Rheumatology Pub Date : 2025-04-01 DOI:10.1093/rheumatology/keae309

Smadar Gertel, May Rokach, Ari Polachek, David Levartovsky, Adi Broyde, Victoria Furer, Tali Ofir Dovrat, Jonathan Wollman, Sara Pel, Yoram Neufeld, Ori Elkayam

{"title":"Ex vivo cell-based assay for assessment of response to TNF inhibitors in patients with rheumatic diseases.","authors":"Smadar Gertel, May Rokach, Ari Polachek, David Levartovsky, Adi Broyde, Victoria Furer, Tali Ofir Dovrat, Jonathan Wollman, Sara Pel, Yoram Neufeld, Ori Elkayam","doi":"10.1093/rheumatology/keae309","DOIUrl":null,"url":null,"abstract":"Objective: There are five TNF inhibitors (TNFis), whose structure and signalling differ. An individual patient with a rheumatic disease may respond to one TNFi but not to another. In addition, 30-40% of patients with rheumatic diseases may respond inadequately to TNFis. The downstream signalling of the various TNFis may determine their clinical efficacy. Several reports have shown that the different TNFis exhibited differential effects on Th17 cells. We analysed the effects of the various TNFis on IL-17A expression in peripheral blood mononuclear cells (PBMCs) of patients with rheumatic diseases, in order to evaluate the possibility of predicting responses in an ex vivo setting.Methods: PBMCs were co-cultured with the various TNFis or medium (control), and IL-17A mRNA levels were analysed by quantitative PCR. IL-17A expression levels in response to four TNFis (not including certolizumab pegol) were compared with that of the control. The IL-17A expression level as determined by the assay was correlated with the clinical response. The assay sensitivity and specificity for distinguishing responders from non-responders was calculated by receiver-operating characteristic (ROC) analysis.Results: The results of the assay for a retrospective cohort of patients with rheumatic diseases (n = 82) correlated with their therapeutic responses to the various TNFis with 89.5% accuracy. Our results indicated that the assay predicted the responses of a prospective cohort (n = 54) to specific TNFis with 79% accuracy.Conclusion: This functional assay could assist in predicting the odds for response to TNFi therapy, indicating whether a given patient is likely to respond to a specific TNFi.","PeriodicalId":21255,"journal":{"name":"Rheumatology","volume":" ","pages":"2233-2241"},"PeriodicalIF":4.7000,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Rheumatology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/rheumatology/keae309","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"RHEUMATOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Objective: There are five TNF inhibitors (TNFis), whose structure and signalling differ. An individual patient with a rheumatic disease may respond to one TNFi but not to another. In addition, 30-40% of patients with rheumatic diseases may respond inadequately to TNFis. The downstream signalling of the various TNFis may determine their clinical efficacy. Several reports have shown that the different TNFis exhibited differential effects on Th17 cells. We analysed the effects of the various TNFis on IL-17A expression in peripheral blood mononuclear cells (PBMCs) of patients with rheumatic diseases, in order to evaluate the possibility of predicting responses in an ex vivo setting.

Methods: PBMCs were co-cultured with the various TNFis or medium (control), and IL-17A mRNA levels were analysed by quantitative PCR. IL-17A expression levels in response to four TNFis (not including certolizumab pegol) were compared with that of the control. The IL-17A expression level as determined by the assay was correlated with the clinical response. The assay sensitivity and specificity for distinguishing responders from non-responders was calculated by receiver-operating characteristic (ROC) analysis.

Results: The results of the assay for a retrospective cohort of patients with rheumatic diseases (n = 82) correlated with their therapeutic responses to the various TNFis with 89.5% accuracy. Our results indicated that the assay predicted the responses of a prospective cohort (n = 54) to specific TNFis with 79% accuracy.

Conclusion: This functional assay could assist in predicting the odds for response to TNFi therapy, indicating whether a given patient is likely to respond to a specific TNFi.

查看原文本刊更多论文

基于体外细胞的检测方法，用于评估风湿病患者对 TNF 抑制剂的反应。

目的：TNF 抑制剂（TNFi）包括 5 种产品，其结构和信号各不相同。个别风湿病患者可能对一种 TNFi 有反应，但对另一种却没有反应。此外，30%-40%的患者对 TNFi 的反应不充分。TNFi下游信号的不同可能导致其临床疗效的不同。一些报告显示，TNFi对Th17细胞有不同的作用。我们分析了 TNFi 对风湿病患者外周血单核细胞（PBMCs）中 IL-17A 表达的不同影响，以评估体内外反应的预测能力：方法：将外周血单核细胞与不同的 TNFi 或培养基（对照组）共同培养，并通过 qPCR 分析 IL-17A mRNA 水平。与对照组相比，IL-17A在4种TNFi（certolizumab pegol除外）反应中的表达水平更高。检测中的 IL-17A 表达与临床反应相关。通过接收器操作特征（ROC）分析计算了区分应答者和非应答者的检测灵敏度和特异性：结果：一组回顾性风湿病患者（n = 82）的检测结果与他们对不同 TNFi 的治疗反应相关，准确率为 89.5%。该测定预测了前瞻性队列（n = 54）对特定 TNFi 的反应，准确率为 79%：该功能测定有助于预测对TNFi疗法的反应几率，表明特定患者是否有可能对特定TNFi产生反应。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Rheumatology 医学-风湿病学

CiteScore

9.40

自引率

7.30%

发文量

1091

审稿时长

2 months

期刊介绍： Rheumatology strives to support research and discovery by publishing the highest quality original scientific papers with a focus on basic, clinical and translational research. The journal’s subject areas cover a wide range of paediatric and adult rheumatological conditions from an international perspective. It is an official journal of the British Society for Rheumatology, published by Oxford University Press. Rheumatology publishes original articles, reviews, editorials, guidelines, concise reports, meta-analyses, original case reports, clinical vignettes, letters and matters arising from published material. The journal takes pride in serving the global rheumatology community, with a focus on high societal impact in the form of podcasts, videos and extended social media presence, and utilizing metrics such as Altmetric. Keep up to date by following the journal on Twitter @RheumJnl.