TY - JOUR
T1 - Transcriptional Profiling of Synovial Macrophages Using Minimally Invasive Ultrasound-Guided Synovial Biopsies in Rheumatoid Arthritis
AU - Mandelin, Arthur M.
AU - Homan, Philip J.
AU - Shaffer, Alexander M.
AU - Cuda, Carla M.
AU - Dominguez, Salina T.
AU - Bacalao, Emily
AU - Carns, Mary
AU - Hinchcliff, Monique
AU - Lee, Jungwha
AU - Aren, Kathleen
AU - Thakrar, Anjali
AU - Montgomery, Anna B.
AU - Bridges, S. Louis
AU - Bathon, Joan M.
AU - Atkinson, John P.
AU - Fox, David A.
AU - Matteson, Eric L.
AU - Buckley, Christopher D.
AU - Pitzalis, Costantino
AU - Parks, Deborah
AU - Hughes, Laura B.
AU - Geraldino-Pardilla, Laura
AU - Ike, Robert
AU - Phillips, Kristine
AU - Wright, Kerry
AU - Filer, Andrew
AU - Kelly, Stephen
AU - Ruderman, Eric M.
AU - Morgan, Vince
AU - Abdala-Valencia, Hiam
AU - Misharin, Alexander V.
AU - Budinger, G. Scott
AU - Bartom, Elizabeth T.
AU - Pope, Richard M.
AU - Perlman, Harris
AU - Winter, Deborah R.
N1 - Publisher Copyright:
© 2018, American College of Rheumatology
PY - 2018/6
Y1 - 2018/6
N2 - Objective: 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. Methods: 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. Results: 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. Conclusion: 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.
AB - Objective: 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. Methods: 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. Results: 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. Conclusion: 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.
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U2 - 10.1002/art.40453
DO - 10.1002/art.40453
M3 - Article
C2 - 29439295
AN - SCOPUS:85046344596
SN - 2326-5191
VL - 70
SP - 841
EP - 854
JO - Arthritis and Rheumatology
JF - Arthritis and Rheumatology
IS - 6
ER -