Good news! Amazing stuff! Hopefully, this will help to come up with effective treatments!
"... To more precisely define cellular drivers of RA, an international research consortium co-led by researchers from the Broad Institute of MIT and Harvard and Brigham and Women’s Hospital analyzed tissues from RA donors at the single-cell level, integrating multiple forms of analysis to stratify RA by six subtypes of inflammation. ...
The findings from the study represent a major milestone in the Accelerating Medicines Partnership Rheumatoid Arthritis and Systemic Lupus Erythematosus program, a public-private partnership launched in 2014 to advance molecular- and cellular-level understandings of autoimmune diseases and identify promising drug targets. ... In particular, the researchers examined tissue from patients with new-onset disease and from patients unresponsive to treatment to better identify both the initial drivers of RA as well as those of refractory disease. ..."
From the abstract:
"Rheumatoid arthritis is a prototypical autoimmune disease that causes joint inflammation and destruction. There is currently no cure for rheumatoid arthritis, and the effectiveness of treatments varies across patients, suggesting an undefined pathogenic diversity. Here, to deconstruct the cell states and pathways that characterize this pathogenic heterogeneity, we profiled the full spectrum of cells in inflamed synovium from patients with rheumatoid arthritis. We used multi-modal single-cell RNA-sequencing and surface protein data coupled with histology of synovial tissue from 79 donors to build single-cell atlas of rheumatoid arthritis synovial tissue that includes more than 314,000 cells. We stratified tissues into six groups, referred to as cell-type abundance phenotypes (CTAPs), each characterized by selectively enriched cell states. These CTAPs demonstrate the diversity of synovial inflammation in rheumatoid arthritis, ranging from samples enriched for T and B cells to those largely lacking lymphocytes. Disease-relevant cell states, cytokines, risk genes, histology and serology metrics are associated with particular CTAPs. CTAPs are dynamic and can predict treatment response, highlighting the clinical utility of classifying rheumatoid arthritis synovial phenotypes. This comprehensive atlas and molecular, tissue-based stratification of rheumatoid arthritis synovial tissue reveal new insights into rheumatoid arthritis pathology and heterogeneity that could inform novel targeted treatments."
Fig. 1: Overview of the multi-modal single-cell synovial tissue pipeline and cell-type abundance analysis that reveals distinct rheumatoid arthritis CTAPs.
No comments:
Post a Comment