Rheumatoid Arthritis New Findings Using Longitudinal Genomics-Monitoring Transcription

New England Journal of Medicine July 16, 2020 pp278-279 Editorial “PRIME Time in Rheumatoid Arthritis” by Ellen M. Gravallese, M.D., and William H. Robinson, M.D., Ph.D.

Expression of Genes in Clusters over Time. See Figure 3C of reference for details.

A summary of and a perspective on the reference paper “RNA Identification of PRIME Cells Predicting Rheumatoid Arthritis Flares ibid pp218-228 D.E. Orange and others.

To date clinical laboratory tests based on reference intervals from cross-sectional studies have not been too useful in predicting Rheumatoid Arthritis (RA) flares in joints. This serial study of RNA expression from an individual’s finger-stick blood specimens “revealed transcriptional signatures in blood that were associated with disease flares…[and helped] identify transcriptional modules representing activation of naïve B cells, which increased in blood approximately 2 weeks before a flare.” “It further allowed for the identification of a new cell type-termed preinflammatory mesenchymal, or PRIME cells-that appeared in blood just before disease flares.” Prime cells then “decreased during the flare, which suggests that these cells may traffic to inflamed synovium and thus represent a circulating precursor of inflammatory synovial fibroblasts.” The involvement of B cells is “consistent with the emerging role for B cells as key drivers of autoimmune and anticancer immune responses.” Based on these findings “it may become possible to intervene to prevent clinical flares…before clinical symptoms emerge”. “This study illustrates the exciting potential of longitudinal genomics to identify key antecedents of disease flares…”

Model from Reference Figure 5.

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