New Research Offers Insight on Potential Therapeutic Targets for Rheumatoid Arthritis, Lupus

Researchers have gleaned new insight into tissue damage related to autoimmune conditions such as rheumatoid arthritis (RA) and lupus, according to 3 new studies published in Nature Immunology.

The findings may lead to the development of potential drug candidates that could advance to experimental treatments, according to the researchers.

The studies, which are part of the Accelerating Medicines Partnership (AMP) on Rheumatoid Arthritis and Systemic Lupus Erythematosus (RA/SLE) program led by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), looked at tissues in which the disease is active in patients. The researchers examined all cell types in either biopsy samples from kidneys of patients with SLE or the synovial tissue of joints from patients with RA.

In the first study, the researchers analyzed individual cells from kidney and skin samples of patients with lupus to examine the mechanisms involved in tissue damage. The analysis showed molecular signatures related to immune system signaling and scar-forming gene activity in kidney cells that may reflect their active role in the disease process.

Because the single cell analysis of skin demonstrated similar changes, the researchers concluded that skin samples may be used in the future as an alternative to more invasive kidney biopsies for monitoring a patient’s disease progression and treatment response.

The second study involved examining the role of immune cells in lupus nephritis. The researchers analyzed kidney, blood, and urine samples from individuals with and without lupus nephritis to understand how immune cells cause progressive damage to the kidneys. Across all samples, the researchers observed subsets of white blood cells active in the disease process, as well as molecules that may serve as potential therapeutic targets.

Lastly, the third study analyzed synovial biopsies to define inflammatory cell states in RA joint tissue. The researchers identified subsets of cells, including fibroblasts, that appear more often in patients with RA. Further research is needed to determine whether these identified cell subsets are involved in tissue inflammation, but their findings could lead to a potential new therapeutic target.

“These AMP rheumatoid arthritis and lupus findings offer insights into intriguing immune system targets that are worthy of more investigation,” Robert Carter, MD, acting director of NIAMS, said in a press release. “We look forward to bringing the most promising of these findings forward to clinical trials, potentially leading to much-needed treatment options for those living with rheumatoid arthritis, lupus, and other immune system disorders.”

Reference

New clues on tissue damage identified in rheumatoid arthritis and lupus [news release]. National Institutes of Health. https://www.nih.gov/news-events/news-releases/new-clues-tissue-damage-identified-rheumatoid-arthritis-lupus. Accessed June 18, 2019.