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.

中文翻译：

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纤维蛋白样坏死的纳入提高了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


尽管早期诊断和治疗，类风湿性关节炎（RA）通常表现出次优的治疗反应。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，并在开始缓解疾病抗风湿药物 (DMARD) 治疗后进行监测。组织学特征[滑膜增生、纤维蛋白样坏死 (FN)、血管过多和炎症浸润]和 IHC（CD3、CD20、CD138、CD68）均按 0-3 等级、7 个级别进行半定量评估。观察到滑膜 CD68 和纤维蛋白样坏死评分之间存在很强的相关性 [r = 0.44 (0.27 − 0.56)； p < 0.0001]。 CD68 与 C 反应蛋白 (CRP)、DAS28、SDAI 和 CDAI 相关。纤维蛋白样坏死评分与 CRP 和 DAS28 相关。然后将患者分为 CD68NecrosisHIGH（CD68 + 坏死≥ 3）和 CD68NecrosisLOW（CD68 + 坏死 < 3）。 CD68NecrosisHIGH 表现出更高的治疗前疾病活动度 [5.48 (1.6) 对比 4.8 (1.7)； p = 0.03]，DAS28 [1.99 (2.06) 对比 1.1 (2.27)，p = 0.03]、SDAI [21.45 (IQR 23.3) 对比 11.65 (IQR 17.5)] 下降幅度更大； p = 0.003] 和 CDAI [16 [14.9] 与 10.5 (20.1)，p = 0.04]。 CD68NecrosisHIGH 患者的 EULAR 中/良好缓解率较高。 CD68Necrosis 评分与临床特征（SJC44 和 DAS28）一起纳入概率矩阵模型，以预测 3 个月时达到中等/良好 EULAR 反应标准并具有良好的表现（AUC 0.724）。 ERA 滑膜活检中的 FN 和 CD68 + 可识别疾病活动度较高的患者，并预测三个月后更好的治疗反应。 包含滑膜 CD68 和纤维蛋白样坏死以及基线临床特征的模型可预测 3 个月时的 EULAR 反应。