Cliniques Universitaires Saint-Luc - Université catholique de Louvain (UCLouvain), Institut de Recherche Expérimentale et Clinique (IREC), Rheumatology, Brussels, Belgium.
Sapienza University of Roma, Rheumatology, Department of Clinical, Internistic, Anesthesiological and Cardiovascular Sciences, Roma, Italy.
Arthritis Res Ther. 2024 Aug 19;26(1):150. doi: 10.1186/s13075-024-03384-9.
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 CD68Necrosis (CD68 + Necrosis ≥ 3) and CD68Necrosis (CD68 + Necrosis < 3). CD68Necrosis 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]. CD68Necrosis 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.
尽管类风湿关节炎（RA）在早期诊断和治疗后，仍经常表现出治疗反应不佳。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，以确定对甲氨蝶呤（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，并在开始使用疾病修饰抗风湿药物（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）、血管过度增生和炎症浸润]和 IHC（CD3、CD20、CD138、CD68）均采用 0-3 分制进行半定量评估，共 7 级。
观察到滑膜 CD68 与纤维蛋白样坏死评分之间存在强烈关联[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 CD68 坏死（CD68+坏死≥3）和 CD68 坏死（CD68+坏死<3）。CD68 坏死患者的治疗前疾病活动度更高[5.48（1.6）与 4.8（1.7）；p=0.03]，DAS28 下降幅度更大[1.99（2.06）与 1.1（2.27），p=0.03]，SDAI[21.45（IQR 23.3）与 11.65（IQR 17.5）；p=0.003]和 CDAI[16 [14.9]与 10.5（20.1）；p=0.04]。CD68 坏死患者的 EULAR 中度/良好反应率更高。CD68 坏死评分与临床特征（SJC44 和 DAS28）一起纳入概率矩阵模型，以预测在 3 个月时达到 EULAR 中度/良好反应标准的可能性，表现良好（AUC 0.724）。
ERA 滑膜活检中的 FN 和 CD68+可识别出疾病活动度较高的患者，并预测在 3 个月时治疗反应更好。包含基线临床特征的滑膜 CD68 和纤维蛋白样坏死的模型可预测 3 个月时的 EULAR 反应。
