Northwestern University Feinberg School of Medicine, Chicago, Illinois.
University of Alabama at Birmingham.
Arthritis Rheumatol. 2018 Jun;70(6):841-854. doi: 10.1002/art.40453. Epub 2018 May 3.
Currently, there are no reliable biomarkers for predicting therapeutic response in patients with rheumatoid arthritis (RA). The synovium may unlock critical information for determining efficacy, since a reduction in the numbers of sublining synovial macrophages remains the most reproducible biomarker. Thus, a clinically actionable method for the collection of synovial tissue, which can be analyzed using high-throughput strategies, must become a reality. This study was undertaken to assess the feasibility of utilizing synovial biopsies as a precision medicine-based approach for patients with RA.
Rheumatologists at 6 US academic sites were trained in minimally invasive ultrasound-guided synovial tissue biopsy. Biopsy specimens obtained from patients with RA and synovial tissue from patients with osteoarthritis (OA) were subjected to histologic analysis, fluorescence-activated cell sorting, and RNA sequencing (RNA-seq). An optimized protocol for digesting synovial tissue was developed to generate high-quality RNA-seq libraries from isolated macrophage populations. Associations were determined between macrophage transcriptional profiles and clinical parameters in RA patients.
Patients with RA reported minimal adverse effects in response to synovial biopsy. Comparable RNA quality was observed from synovial tissue and isolated macrophages between patients with RA and patients with OA. Whole tissue samples from patients with RA demonstrated a high degree of transcriptional heterogeneity. In contrast, the transcriptional profile of isolated RA synovial macrophages highlighted different subpopulations of patients and identified 6 novel transcriptional modules that were associated with disease activity and therapy.
Performance of synovial tissue biopsies by rheumatologists in the US is feasible and generates high-quality samples for research. Through the use of cutting-edge technologies to analyze synovial biopsy specimens in conjunction with corresponding clinical information, a precision medicine-based approach for patients with RA is attainable.
目前，尚无可靠的生物标志物可用于预测类风湿关节炎（RA）患者的治疗反应。滑膜可能为确定疗效提供关键信息，因为减少滑膜下巨噬细胞的数量仍然是最具重现性的生物标志物。因此，必须实现一种用于收集滑膜组织的临床可行方法，该方法可以使用高通量策略进行分析。本研究旨在评估利用滑膜活检作为 RA 患者基于精准医学的方法的可行性。
6 家美国学术机构的风湿病学家接受了微创超声引导下滑膜组织活检的培训。对 RA 患者的活检标本和 OA 患者的滑膜组织进行组织学分析、荧光激活细胞分选和 RNA 测序（RNA-seq）。开发了一种优化的滑膜组织消化方案，用于从分离的巨噬细胞群体中生成高质量的 RNA-seq 文库。确定了 RA 患者中巨噬细胞转录谱与临床参数之间的关联。
RA 患者对滑膜活检的不良反应极小。RA 和 OA 患者的滑膜组织和分离的巨噬细胞的 RNA 质量相当。RA 患者的全组织样本显示出高度的转录异质性。相比之下，分离的 RA 滑膜巨噬细胞的转录谱突出了不同的患者亚群，并确定了与疾病活动度和治疗相关的 6 个新的转录模块。
美国风湿病学家进行滑膜组织活检是可行的，并可生成用于研究的高质量样本。通过使用先进的技术来分析滑膜活检标本并结合相应的临床信息，可以实现 RA 患者的精准医学方法。
