Abstract
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 as reduction in numbers of sublining synovial macrophages remains the most reproducible biomarker. Thus, a clinically actionable method for collection of synovial tissue, which can be analyzed using high-throughput strategies, must become a reality.
Methods:
Rheumatologists at six United States academic sites were trained in minimally
invasive ultrasound-guided synovial tissue biopsy. Histology, fluorescence-activated cell sorting and RNA-seq were performed on biopsy synovial tissue from patients with RA and compared with osteoarthritis (OA) samples. 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 of RA patients.
Results:
Patients with RA reported minimal adverse effects in response to synovial biopsy.
Comparable RNA quality was observed between synovial tissue and isolated macrophages from patients with RA and 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 a subpopulation of patients and identified six novel
transcriptional modules that were associated with disease activity and therapy.
Conclusion: Performance of synovial tissue biopsies by rheumatologists in the United States is feasible and generates high-quality samples for research. By utilizing cutting-edge technologies on synovial biopsies with corresponding clinical information, a precision-based medicine approach for patients with RA is attainable.
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 as reduction in numbers of sublining synovial macrophages remains the most reproducible biomarker. Thus, a clinically actionable method for collection of synovial tissue, which can be analyzed using high-throughput strategies, must become a reality.
Methods:
Rheumatologists at six United States academic sites were trained in minimally
invasive ultrasound-guided synovial tissue biopsy. Histology, fluorescence-activated cell sorting and RNA-seq were performed on biopsy synovial tissue from patients with RA and compared with osteoarthritis (OA) samples. 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 of RA patients.
Results:
Patients with RA reported minimal adverse effects in response to synovial biopsy.
Comparable RNA quality was observed between synovial tissue and isolated macrophages from patients with RA and 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 a subpopulation of patients and identified six novel
transcriptional modules that were associated with disease activity and therapy.
Conclusion: Performance of synovial tissue biopsies by rheumatologists in the United States is feasible and generates high-quality samples for research. By utilizing cutting-edge technologies on synovial biopsies with corresponding clinical information, a precision-based medicine approach for patients with RA is attainable.
| Original language | English |
|---|---|
| Journal | Arthritis and Rheumatology |
| Early online date | 13 Feb 2018 |
| DOIs | |
| Publication status | E-pub ahead of print - 13 Feb 2018 |