Rheumatoid arthritis (RA) is an autoimmune disease that causes joint inflammation, pain, and stiffness. There are several treatment options to control inflammation, but response to therapy varies and some people with RA never reach remission, suggesting there may be different drivers of inflammation. 

In a study recently published in Nature, a team of researchers studied more than 314,000 cells from samples of synovial tissues—specialized tissues that lubricate and cushion the joint but become inflamed in RA. The team identified six major types of inflammation and categorized them into groups known as cell-type abundance phenotypes (CTAPs). Many of the CTAPs had an abundance of cells normally associated with inflammatory responses; however, some contained cells generally associated with other cellular functions.

To better understand how each CTAP might contribute to inflammation, the researchers characterized their cell states; these cell states are reflected by the genes and proteins that cells express at a given time, which allow them to engage in specialized functions. Cell state analysis offered insight into the molecular pathways driving inflammation and contributing to RA. The researchers also observed that these CTAPs were associated with certain chemical messengers that control the inflammatory response. Importantly, some biologic therapies for RA altered the CTAPs over time. 

This study highlights the diversity of inflammation in people with RA and may inform the development of more tailored RA treatments.  Future studies are needed to determine if researchers can expand these findings to other inflammatory diseases. 

This research was supported by the Accelerating Medicines Partnership® Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP® RA/SLE) Program, which was funded in part by NIAMS.

Zhang, F, Jonsson, AH, Nathan, A et al. Deconstruction of rheumatoid arthritis synovium defines inflammatory subtypes. Nature. 2023. https://doi.org/10.1038/s41586-023-06708-y