Treating RA Via Synovial Fibroblasts

The results are “extremely promising” say UK researchers with regard to their efforts to locate new therapeutic targets for the treatment of rheumatoid arthritis (RA). A study led by researchers at the University of Birmingham’s Institute of Inflammation and Ageing looked at synovial fibroblasts (SFs) in RA patients. As indicate in the November 23, 2016 news release, “In RA patients, SF cells cause damage by invading and attacking the cartilage and bone around the joint.”

“The scientists identified two distinct types of SF within the synovial membrane. The team showed that these cell types, defined by the presence of specific cell surface markers (PDPN and CD248), aggregate in different layers of the synovium, and just one (the PDPN type) is responsible for cartilage damage in RA patients.”

Adam Croft, Ph.D., who led the research, told OTW, “Fibroblasts are key effector cells in both driving joint inflammation and causing structural joint damage and deformity. Despite their key role in joint pathology these cells are yet to be targeted therapeutically.”

“Our current treatments for rheumatoid arthritis aim to target leucocytes (white blood cells) and their derived products. Whilst effective, these treatments result in immune suppression increasing the risk of infection. In addition, 30% of patients develop refractory disease despite treatment and many more fail to achieve disease remission. More targeted treatments could reduce the risk of adverse events and immune suppression and increase the effectiveness of therapy by directly targeting cells directly involved in joint pathology at different stages in the natural history of the disease.”

“We identified cell surface proteins that distinguished fibroblasts with distinct anatomical compartments of the synovial membrane. Aggressive fibroblasts were found within the lining layer of the synovium and could be identified by the expression of the cell surface protein podoplanin. These cells invaded cartilage and were able to travel in the blood stream and destroy cartilage at distant sites of cartilage implantation. This raises the possibility that pathogenic populations of fibroblasts exist that result in structural joint damage that can be identified by their expression of distinct cell surface proteins.”

“We are now performing pre-clinical experimental studies to develop strategies to selectively target these pathogenic subsets of fibroblasts and further understand their role in inflammatory joint pathology.”