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Tissue analysis with cytometry may help develop new RA therapies
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SAN DIEGO – A novel tool that uses cytometry to assess the cellular and molecular profiles of synovial tissue and peripheral blood may lead to better therapies for rheumatoid arthritis, according to data presented at the 2017 American College of Rheumatology meeting.
The Accelerated Medicines Partnership program’s RA Network of researchers has completed phase 1 of a project that used cellular and molecular profiling of synovial tissue and matched peripheral blood from patients with RA in the U.S. to learn more about the disease.
“The emerging data from phase 1 of this study is very encouraging. We see that, in addition to being able to numerate distinct inflammatory cell types in the cell tissue, we’re now able to visualize thousands of gene expressions at a single cell level,” lead author Kevin Wei, MD, PhD, instructor at Brigham and Women’s Hospital, said during his presentation. “For the first time, we’re able to do this analysis on samples derived from biopsies of patients with RA in contrast to tissue obtained from patients undergoing surgery.”
In this prospective, observational study, researchers analyzed 58 synovial tissues from 22 biopsies, and 20 RA and 16 osteoarthritis elective surgical procedures, using a combination of flow cytometry, mass cytometry and RNA sequencing. They recruited U.S. patients with RA aged 18 years and older who had at least one inflamed joint from 10 contributing sites in the network. They then assessed the quality of the synovial tissue and graded the level of synovitis.
Synovial cellular composition obtained by flow cytometry and mass cytometry were highly consistent in T cells (r = 0.98), B cells (r = 0.96), myeloid cells (r = 0.64), endothelial cells (r = 0.81) and synovial fibroblasts (r=0.93), which supports synovial analysis by mass cytometry of synovial tissue.
In contrast, RA synovial tissue taken from elective surgical procedures showed varied degrees of inflammation with mean Krenn inflammation score (0-3) of 0.94, and the tissue obtained from biopsies showed higher Krenn inflammation scores compared with OA (1.68 vs. 0.73; P = .02) and greater quantity of lymphocytes by flow cytometry (67% vs. 8%; P < .001). This infiltration of lymphocytes in the tissue assessed by cytometry was significantly correlated with histologic inflammation score (P < .001), further validating the efficiency of flow cytometric assessment.
Component analysis of synovial cell flow cytometry data identified three RA arthroplasty samples with inflammatory features similar to those observed in RA biopsies. These samples also showed higher inflammation score of inflammation by histology (2 vs. 0.77; P < .001). Ongoing transcriptomic profiling of synovial cells from these samples shows molecular heterogeneity in RA synovium.
These findings help lay the ground work for future phase 2 research, according to the researchers.
“Looking to the future, phase 2 of the consortium is underway. Here, we’re trying to test whether this technology, and also the newer technology, can then be applied to a much larger cohort of patients,” Wei said in his presentation. “We’ll include up to 120 patients for our study. We’ll apply newer technology that can allow us to see as much as 100 times more cells and 3,000 genes at a time of all the molecular pathways involved in RA. We’re very excited and look forward to sharing over the next couple of years.” – by Savannah Demko
Reference:
Wei K, et al. #1405. Presented at: American College of Radiology Annual Meeting; Nov. 4-8, 2017; San Diego.
Disclosures: Wei reports disclosures from Roche Pharmaceuticals. Please see the study for all other authors’ relevant financial disclosures.