2023-11-16 09:00:00
Researchers from an international research consortium have analyzed more than 314,000 cells from rheumatoid arthritis tissue and have defined six types of inflammation that involve various cell types and disease pathways, as published in the journal ‘Nature’. Understanding the disease at the single-cell level can drive the development of specific drugs and treatment strategies. Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation that causes pain, joint damage and disability, and which It affects approximately 18 million people worldwide.
Although RA therapies targeting specific inflammatory pathways have emerged, only some patients improve their symptoms with treatment, underscoring the need for multiple therapeutic approaches tailored to different subtypes of the disease. To more precisely define the cellular factors of RA, an international research consortium co-led by researchers from the Broad Institute of the Massachusetts Institute of Technology (MIT), Harvard University, and Brigham and Women’s Hospital, in the United States, analyzed tissues from donors with RA at the single-cell level, integrating multiple forms of analysis to stratify RA into six subtypes of inflammation. The results shed new light on the variety of cellular causes of RA, which may serve as a basis for more specific, effective and patient-tailored therapeutic approaches. ‘In treating people with rheumatoid arthritis, we strive to find the right treatment for each patient,’ said study author Dr. Soumya Raychaudhuri, a member of the Broad Institute and the Brigham’s Division of Rheumatology, Inflammation and Immunity. ‘We set out to determine why some subsets of patients do not respond to conventional treatments by analyzing inflammation subtypes –continues–. We did it from many different angles, using multiple cutting-edge single-cell techniques and integrating the results in a way that had not been done before for an inflammatory disease.’
Study results
The study results 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 understanding of autoimmune diseases and identify promising drug targets. Working with researchers and doctors in the United States and the United Kingdom, the researchers analyzed 79 samples of donor synovial tissue, the inflamed RA tissue that normally helps cushion and support joints. Specifically, the researchers examined tissue from patients with new-onset disease and from patients who did not respond to treatment to better identify both the initial factors of RA and those of refractory disease. To ‘deconstruct’ RA pathology at the cellular level, the researchers combined data from surface proteins and histological analyzes with multiple forms of single-cell RNA sequencing and bulk RNA sequencing.
Cell type abundance phenotypes
Despite the variety of methods used to analyze more than 314,000 cells, the researchers consistently found evidence of six main types of inflammation, which they stratified by associated cell type, called cell type abundance phenotypes (CTAP).
Although some CTAPS, such as those enriched in T and B cells, were expected findings in an autoimmune disease such as RA, the researchers were surprised to see CTAPs associated with structural cells such as fibroblasts and endothelial cells, with relatively few inflammatory leukocytes. They also found that patients’ CTAPs were dynamic and might change over time in response to treatment. Looking ahead, researchers aim to expand their knowledge of the cell types involved in RA by studying how interconnections between cells promote disease states. Besides, They hope that this work will encourage further analysis of synovial tissue in patients with RA, which is currently not common practice. Although blood tests are more common in RA patients, the results of this study and others highlight that the cellular profile of synovial tissue differs substantially from that of blood. ‘This study shows that tissue matters,’ said Dr. Michael Brenner, co-senior author of the study and a member of the Brigham’s Division of Rheumatology, Inflammation and Immunity. ‘Our findings point to the value of obtaining biopsies of synovial tissue to evaluate the nature of the pathological process, which can be so different in different patients,’ he emphasizes. In the future, clinical trials will benefit greatly from evaluating tissue characteristics along with responses to a therapy.’ ‘With this atlas of the cell types and pathways involved in RA, we are better able to pursue our precision medicine goal of being able to select the right drug for the right patient and achieve a high response rate,’ he concludes. .
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