RNA Identification of PRIME Cells Predicting Rheumatoid Arthritis Flares.

The New England Journal of Medicine
Dana E OrangeRobert B Darnell

Abstract

Rheumatoid arthritis, like many inflammatory diseases, is characterized by episodes of quiescence and exacerbation (flares). The molecular events leading to flares are unknown. We established a clinical and technical protocol for repeated home collection of blood in patients with rheumatoid arthritis to allow for longitudinal RNA sequencing (RNA-seq). Specimens were obtained from 364 time points during eight flares over a period of 4 years in our index patient, as well as from 235 time points during flares in three additional patients. We identified transcripts that were differentially expressed before flares and compared these with data from synovial single-cell RNA-seq. Flow cytometry and sorted-blood-cell RNA-seq in additional patients were used to validate the findings. Consistent changes were observed in blood transcriptional profiles 1 to 2 weeks before a rheumatoid arthritis flare. B-cell activation was followed by expansion of circulating CD45-CD31-PDPN+ preinflammatory mesenchymal, or PRIME, cells in the blood from patients with rheumatoid arthritis; these cells shared features of inflammatory synovial fibroblasts. Levels of circulating PRIME cells decreased during flares in all 4 patients, and flow cytometry and sorte...Continue Reading

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Citations

Jul 16, 2020·The New England Journal of Medicine·Ellen M Gravallese, William H Robinson
Jul 30, 2020·Nature Reviews. Rheumatology·Joanna Clarke
Oct 22, 2020·The New England Journal of Medicine·Cong-Qiu Chu
Dec 10, 2020·Nature Reviews. Rheumatology·Maya H BuchDennis McGonagle
Jan 20, 2021·Arthritis Research & Therapy·Matthew WrightDamini Jawaheer
Dec 29, 2020·Plastic and Reconstructive Surgery·Brett T PhillipsArun K Gosain
Jan 5, 2021·Frontiers in Immunology·K Michael Pollard
Feb 23, 2021·Frontiers in Immunology·Emmanuel WeissRichard Moreau
Mar 16, 2021·Frontiers in Immunology·Michelle L RobinettePaul A Monach
Jun 8, 2021·Immunological Reviews·Lucy-Jayne MarshAdam P Croft
Jul 9, 2021·Zeitschrift für Rheumatologie·Gerd-Rüdiger BurmesterThomas Rose
Jun 10, 2021·Arthritis & Rheumatology·Carlos de la Calle-FabregatEsteban Ballestar

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