HealthDay News — Distinct RNA signatures are evident in peripheral blood of rheumatoid arthritis patients before a disease flare, according to a study published in the New England Journal of Medicine.
Dana E. Orange, MD, from the Rockefeller University in New York City, and colleagues established a clinical and technical protocol for repeated home collection of blood in rheumatoid arthritis patients to allow for longitudinal RNA sequencing (RNA-seq). In an index patient, specimens were obtained from 364 time points during 8 flares over a period of 4 years; in 3 additional patients, specimens were obtained from 235 time points during flares. Transcripts that were differentially expressed before flares were identified and compared to data from synovial single cell RNA-seq.
The researchers identified consistent changes in blood transcriptional profiles 1 to 2 weeks before a rheumatoid arthritis flare. In the blood of patients with rheumatoid arthritis, B-cell activation was followed by expansion of circulating CD45-CD31-PDPN+ preinflammatory mesenchymal or PRIME cells, which shared features of inflammatory synovial fibroblasts. In all four patients, levels of circulating PRIME cells decreased during flares; in 19 additional patients with rheumatoid arthritis, flow cytometry and sorted-cell RNA-seq confirmed the presence of PRIME cells.
“We suggest that before a clinical flare, B-cell immune activation (detected as antecedent cluster [AC] 2) acts on PRIME cells, which traffic to the blood (detected as AC3) and subsequently to the synovial sublining during flares of disease activity,” the authors write.