Inclusion of fibrinoid necrosis increases the accuracy of synovial tissue assessment in predicting response to methotrexate: analysis of the UCLouvain Brussels ERA Cohort

IF 4.9 2区医学 Q1 Medicine

Arthritis Research & Therapy Pub Date : 2024-08-19 DOI:10.1186/s13075-024-03384-9

Francesco Natalucci, Clément Triaille, Cécile Van Mullem, Tatiana Sokolova, Emilie Sapart, Laurent Meric de Bellefon, Adrien Nzeusseu, Christine Galant, Bernard Lauwerys, Patrick Durez

{"title":"Inclusion of fibrinoid necrosis increases the accuracy of synovial tissue assessment in predicting response to methotrexate: analysis of the UCLouvain Brussels ERA Cohort","authors":"Francesco Natalucci, Clément Triaille, Cécile Van Mullem, Tatiana Sokolova, Emilie Sapart, Laurent Meric de Bellefon, Adrien Nzeusseu, Christine Galant, Bernard Lauwerys, Patrick Durez","doi":"10.1186/s13075-024-03384-9","DOIUrl":null,"url":null,"abstract":"Rheumatoid Arthritis (RA) often exhibits suboptimal treatment response despite early diagnosis and treatment. This study aimed to analyze Early Rheumatoid Arthritis (ERA) synovial biopsies through histology and immunohistochemistry (IHC) to identify predictive factors for treatment response to Methotrexate (MTX). 140 ERA patients from the UCLouvain Arthritis Cohort underwent synovial biopsy and were monitored after initiating Disease-Modifying Antirheumatic Drug (DMARD) therapy. Histological features [Synovial Hyperplasia, Fibrinoid Necrosis (FN), Hypervascularization and Inflammatory Infiltrate] and IHC (CD3, CD20, CD138, CD68) were each semi-quantitatively assessed on a 0–3 scale with 7 levels. A strong association was observed between synovial CD68 and Fibrinoid Necrosis scores [r = 0.44 (0.27 − 0.56); p < 0.0001]. CD68 correlated with C-Reactive Protein (CRP), DAS28, SDAI and CDAI. Fibrinoid Necrosis score correlated with CRP and DAS28. Patients were then categorized as CD68NecrosisHIGH (CD68 + Necrosis ≥ 3) and CD68NecrosisLOW (CD68 + Necrosis < 3). CD68NecrosisHIGH exhibited higher pre-treatment disease activity [5.48 (1.6) versus 4.8 (1.7); p = 0.03] and a greater fall in DAS28 [1.99 (2.06) versus 1.1 (2.27), p = 0.03], SDAI [21.45 (IQR 23.3) versus 11.65 (IQR 17.5); p = 0.003] and CDAI [16 [14.9] versus 10.5 (20.1), p = 0.04]. CD68NecrosisHIGH patients had a higher EULAR Moderate/Good Response rate. CD68Necrosis score was incorporated into a probability matrix model together with clinical features (SJC44 and DAS28) to predict achieving a Moderate/Good EULAR Response Criteria at 3 months with a good performance (AUC 0.724). FN and CD68 + in ERA synovial biopsies identify patients with higher disease activity and predict a better treatment response at three months. A model including synovial CD68 and fibrinoid necrosis with baseline clinical features predicts EULAR response at 3 months.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":null,"pages":null},"PeriodicalIF":4.9000,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Arthritis Research & Therapy","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1186/s13075-024-03384-9","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Medicine","Score":null,"Total":0}

引用次数: 0

Abstract

Rheumatoid Arthritis (RA) often exhibits suboptimal treatment response despite early diagnosis and treatment. This study aimed to analyze Early Rheumatoid Arthritis (ERA) synovial biopsies through histology and immunohistochemistry (IHC) to identify predictive factors for treatment response to Methotrexate (MTX). 140 ERA patients from the UCLouvain Arthritis Cohort underwent synovial biopsy and were monitored after initiating Disease-Modifying Antirheumatic Drug (DMARD) therapy. Histological features [Synovial Hyperplasia, Fibrinoid Necrosis (FN), Hypervascularization and Inflammatory Infiltrate] and IHC (CD3, CD20, CD138, CD68) were each semi-quantitatively assessed on a 0–3 scale with 7 levels. A strong association was observed between synovial CD68 and Fibrinoid Necrosis scores [r = 0.44 (0.27 − 0.56); p < 0.0001]. CD68 correlated with C-Reactive Protein (CRP), DAS28, SDAI and CDAI. Fibrinoid Necrosis score correlated with CRP and DAS28. Patients were then categorized as CD68NecrosisHIGH (CD68 + Necrosis ≥ 3) and CD68NecrosisLOW (CD68 + Necrosis < 3). CD68NecrosisHIGH exhibited higher pre-treatment disease activity [5.48 (1.6) versus 4.8 (1.7); p = 0.03] and a greater fall in DAS28 [1.99 (2.06) versus 1.1 (2.27), p = 0.03], SDAI [21.45 (IQR 23.3) versus 11.65 (IQR 17.5); p = 0.003] and CDAI [16 [14.9] versus 10.5 (20.1), p = 0.04]. CD68NecrosisHIGH patients had a higher EULAR Moderate/Good Response rate. CD68Necrosis score was incorporated into a probability matrix model together with clinical features (SJC44 and DAS28) to predict achieving a Moderate/Good EULAR Response Criteria at 3 months with a good performance (AUC 0.724). FN and CD68 + in ERA synovial biopsies identify patients with higher disease activity and predict a better treatment response at three months. A model including synovial CD68 and fibrinoid necrosis with baseline clinical features predicts EULAR response at 3 months.

查看原文本刊更多论文

纳入纤维素性坏死可提高滑膜组织评估在预测甲氨蝶呤反应方面的准确性：对 UCLouvain 布鲁塞尔 ERA 队列的分析

类风湿性关节炎（RA）尽管可以早期诊断和治疗，但其治疗反应往往不尽如人意。本研究旨在通过组织学和免疫组织化学（IHC）分析早期类风湿性关节炎（ERA）滑膜活检，以确定甲氨蝶呤（MTX）治疗反应的预测因素。来自 UCLouvain 关节炎队列的 140 名ERA 患者接受了滑膜活检，并在开始使用改变病情抗风湿药（DMARD）治疗后接受了监测。组织学特征[滑膜增生、纤溶性坏死（FN）、血管增生和炎性浸润]和 IHC（CD3、CD20、CD138、CD68）均按 0-3 级的 7 个等级进行半定量评估。滑膜 CD68 与纤溶坏死评分之间存在密切联系[r = 0.44 (0.27 - 0.56); p < 0.0001]。CD68与C反应蛋白（CRP）、DAS28、SDAI和CDAI相关。纤溶坏死评分与 CRP 和 DAS28 相关。然后将患者分为 CD68NecrosisHIGH（CD68 + 坏死≥ 3）和 CD68NecrosisLOW（CD68 + 坏死< 3）两类。CD68NecrosisHIGH 在治疗前表现出更高的疾病活动度 [5.48 (1.6) 对 4.8 (1.7); p = 0.03]，DAS28 下降幅度更大 [1.99 (2. 06) 对 1.1 (2. 06)]。06) 对 1.1 (2.27), p = 0.03]、SDAI [21.45 (IQR 23.3) 对 11.65 (IQR 17.5); p = 0.003]和 CDAI [16 [14.9] 对 10.5 (20.1), p = 0.04]。CD68NecrosisHIGH 患者的 EULAR 中度/良好反应率更高。CD68Necrosis评分与临床特征（SJC44和DAS28）一起被纳入概率矩阵模型，以预测3个月后达到EULAR中度/良好反应标准的情况，效果良好（AUC 0.724）。ERA滑膜活检中的FN和CD68 +可识别疾病活动性较高的患者，并预测3个月后的治疗反应。包括滑膜 CD68 和纤维坏死以及基线临床特征在内的模型可预测 3 个月后的 EULAR 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

Arthritis Research & Therapy RHEUMATOLOGY-

CiteScore

8.60

自引率

2.00%

发文量

261

审稿时长

14 weeks

期刊介绍： Established in 1999, Arthritis Research and Therapy is an international, open access, peer-reviewed journal, publishing original articles in the area of musculoskeletal research and therapy as well as, reviews, commentaries and reports. A major focus of the journal is on the immunologic processes leading to inflammation, damage and repair as they relate to autoimmune rheumatic and musculoskeletal conditions, and which inform the translation of this knowledge into advances in clinical care. Original basic, translational and clinical research is considered for publication along with results of early and late phase therapeutic trials, especially as they pertain to the underpinning science that informs clinical observations in interventional studies.