Associations Between Rheumatoid Arthritis Clinical Factors and Synovial Cell Types and States

IF 11.4 1区医学 Q1 RHEUMATOLOGY

Arthritis & Rheumatology Pub Date : 2023-10-04 DOI:10.1002/art.42726

Dana Weisenfeld, Fan Zhang, Laura Donlin, Anna Helena Jonsson, William Apruzzese, Debbie Campbell, Accelerating Medicines Partnership Program: RA/SLE Network, Deepak A. Rao, Kevin Wei, V. Michael Holers, Ellen Gravallese, Larry Moreland, Susan Goodman, Michael Brenner, Soumya Raychaudhuri, Andrew Filer, Jennifer Anolik, Vivian Bykerk, Katherine P. Liao

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引用次数: 0

Abstract

Objective

Recent studies have uncovered diverse cell types and states in the rheumatoid arthritis (RA) synovium; however, limited data exist correlating these findings with patient-level clinical information. Using the largest cohort to date with clinical and multicell data, we determined associations between RA clinical factors with cell types and states in the RA synovium.

Methods

The Accelerated Medicines Partnership Rheumatoid Arthritis study recruited patients with active RA who were not receiving disease-modifying antirheumatic drugs (DMARDs) or who had an inadequate response to methotrexate (MTX) or tumor necrosis factor inhibitors. RA clinical factors were systematically collected. Biopsies were performed on an inflamed joint, and tissue were disaggregated and processed with a cellular indexing of transcriptomes and epitopes sequencing pipeline from which the following cell type percentages and cell type abundance phenotypes (CTAPs) were derived: endothelial, fibroblast, and myeloid (EFM); fibroblasts; myeloid; T and B cells; T cells and fibroblasts (TF); and T and myeloid cells. Correlations were measured between RA clinical factors, cell type percentage, and CTAPs.

Results

We studied 72 patients (mean age 57 years, 75% women, 83% seropositive, mean RA duration 6.6 years, mean Disease Activity Score-28 C-reactive Protein 3 [DAS28-CRP3] score 4.8). Higher DAS28-CRP3 correlated with a higher T cell percentage (P < 0.01). Those receiving MTX and not a biologic DMARD (bDMARD) had a higher percentage of B cells versus those receiving no DMARDs (P < 0.01). Most of those receiving bDMARDs were categorized as EFM (57%), whereas none were TF. No significant difference was observed across CTAPs for age, sex, RA disease duration, or DAS28-CRP3.

Conclusion

In this comprehensive screen of clinical factors, we observed differential associations between DMARDs and cell phenotypes, suggesting that RA therapies, more than other clinical factors, may impact cell type/state in the synovium and ultimately influence response to subsequent therapies.

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类风湿性关节炎临床因素与滑膜细胞类型和状态的关系。

目的：最近的研究揭示了RA滑膜中不同的细胞类型/状态；然而，将这些发现与患者水平的临床信息相关联的数据有限。使用迄今为止最大的临床和多细胞数据队列，我们确定了RA临床因素与RA滑膜细胞类型/状态之间的相关性。方法：Accelerated Medicines Partnership类风湿关节炎研究招募了无DMARD或对甲氨蝶呤（MTX）或肿瘤坏死因子抑制剂反应不足的活动性RA受试者。系统收集RA临床因素。对发炎的关节和组织进行活检，并用CITE-seq管道分解和处理组织，从中获得细胞类型百分比和细胞类型丰度表型（CTAP）：内皮/成纤维细胞/髓细胞（EFM）、成纤维细胞（F）、髓细胞（M）、T/B细胞（TB）、T细胞/成纤维纤维细胞（TF）、T/髓细胞（TM）。测量RA临床因素、%细胞类型和CTAP之间的相关性。结果：我们研究了72名受试者，平均年龄57岁年，75%女性，83%血清阳性，平均RA持续时间6.6 年，平均DAS28-CRP3 4.8。较高的DAS28-CRP3与较高的%T细胞相关（结论：在这项临床因素的全面筛选中，我们观察到DMARD与细胞表型之间的差异关联，这表明RA治疗比其他临床因素更可能影响滑膜中的细胞类型/状态，并最终影响对后续治疗的反应。本文受版权保护。保留所有权利。）。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Arthritis & Rheumatology RHEUMATOLOGY-

CiteScore

20.90

自引率

3.00%

发文量

371

期刊介绍： Arthritis & Rheumatology is the official journal of the American College of Rheumatology and focuses on the natural history, pathophysiology, treatment, and outcome of rheumatic diseases. It is a peer-reviewed publication that aims to provide the highest quality basic and clinical research in this field. The journal covers a wide range of investigative areas and also includes review articles, editorials, and educational material for researchers and clinicians. Being recognized as a leading research journal in rheumatology, Arthritis & Rheumatology serves the global community of rheumatology investigators and clinicians.