Session Description: 

Thursday April 21, 2022
4:30-5:40 pm EDT

Dr. Dana Orange
Rockefeller University & Hospital for Special Surgery, New York

"A personalized approach to rheumatoid arthritis flares"

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. Flow cytometry and sorted-cell RNA-seq confirmed the presence of PRIME cells in additional patients with rheumatoid arthritis. Longitudinal genomic analysis of rheumatoid arthritis flares revealed PRIME cells in the blood during the period before a flare and suggested a model in which these cells become activated by B cells in the weeks before a flare and subsequently migrate out of the blood into the synovium. 

Bio: Dr. Dana Orange, MD, MSc, is an Assistant Professor at Rockefeller University and Assistant Attending of Rheumatology at the Hospital for Special Surgery. She received her medical degree from Weill Cornell Medical College, Cornell University, and her MSc from Rockefeller University. She completed her Internal Medicine Residency at New York Presbyterian Hospital and her Rheumatology Fellowship at the Hospital for Special Surgery. Dr. Orange’s research aims to understand the molecular underpinnings of symptoms of rheumatoid arthritis such as pain, morning stiffness, and flares

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