Research supported by the Accelerating Medicines Partnership (AMP) on Rheumatoid Arthritis and Systemic Lupus Erythematosus (RA/SLE) has revealed new clues on tissue damage identified in rheumatoid arthritis and lupus.
Findings include the identification of novel molecular signatures related to immune system signaling in kidney cells that may reflect their active role in disease process; molecular targets, including specific white blood cells, for potential treatment in lupus nephritis; and specific types of fibroblasts and white blood cells that are involved in rheumatoid arthritis. These discoveries set the stage for uncovering potential drug target candidates that could advance to experimental treatments. Results of the studies were published today in three papers in Nature Immunology.
AMP is laying the foundation for precision medicine in rheumatoid arthritis and lupus,” said NIH Director Dr. Francis S. Collins, M.D., Ph.D. “The public and private sector working together has sparked new hope for those living with these and other autoimmune diseases, and we anticipate that these early results are only the beginning of what is serving as a new model to transform medical care.”
A primary goal of the AMP RA/SLE program, which is led by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), is to study tissues where the disease is active in patients, whereas most previous work studied mouse models or only blood samples from humans. AMP researchers looked at all the cell types in either biopsy samples from kidneys of people with SLE or the synovial tissues of joints from people with RA. The program seeks to quickly find the most promising treatment targets so less time is lost chasing unsuccessful leads.
Profiling kidney and skin cells in lupus nephritis. Lupus nephritis is a potentially fatal kidney disease that occurs in about 50% of people with lupus. There can be a wide variety of changes in the kidneys, making the disease hard to diagnose and treat. AMP investigators led by co-senior investigator Jill Buyon, M.D., at New York University analyzed a large number of individual cells from kidney and skin samples from people with lupus in order to understand more about the complex mechanisms involved in tissue damage. Researchers discovered molecular signatures, related to immune system signaling and scar-forming gene activity, in kidney cells that may reflect their active role in disease process. This finding was unexpected since inflammatory cells were thought to be the primary cause of tissue damage. Single cell analysis of skin revealed similar changes, suggesting that in the future it may be possible to monitor a person’s disease progress and treatment responses from skin samples instead of more invasive kidney biopsies
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