Newly discovered PRIME cells act as a warning signal for Rhe
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A newly discovered type of cell could one day help rheumatoid arthritis patients predict the onset of painful flare-ups of the disease. The new discovery could potentially lead to a future blood test that could warn patients of a coming flare or could also be a potential target for drugs,

Researchers 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 the index patient, as well as from 235 time points during flares in three additional patients.

They 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.

Results:
- 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. Based on RNA expression profiles, they found these cells to be strikingly similar to synovial fibroblasts, which are found in the tissue linings of joints.
- Levels of circulating PRIME cells decreased during flares in all 4 patients, and flow cytometry and sorted-cell RNA-seq confirmed the presence of PRIME cells in 19 additional patients with rheumatoid arthritis.

Conclusively, 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.

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2004114?query=featured_home
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