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Study identifies potential new target for RA treatment

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New research on role of fibroblasts in rheumatoid arthritis (RA) could lead to more targeted treatments.

The study, published in the journal Arthritis Research and Therapy, focuses on synovial fibroblasts (SFs) — cells that make up part of the connective tissue, or synovium, around human joints. In RA patients, SF cells cause damage by invading and attacking the cartilage and bone around the joint.

Researchers at the University of Birmingham examined the role of different types of fibroblast cells in the development of RA, and identified two distinct types of SFs within the synovial membrane. The study demonstrated 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.

Tests showed that the ‘lining’ layer of an artificial synovium (i.e. the part closest to the cartilage) contained invasive PDPN type SFs, while the part that was further away from the cartilage contained the non-invasive CD248 type.

The study also revealed that PDPN type SF cells were the first to migrate to attack other cartilage in the body, with CD248 cells only appearing in secondary tissue at a later stage.

Dr Adam Croft from the University of Birmingham, who led the research, said: “This study not only shows the existence of distinct sub-sets of synovial fibroblasts, but also suggests that these cells are able to self-organise into lining and sub-lining layers in the presence of cartilage. Combined with the difference in migration rates between the two types of cell, these results are extremely promising in terms of finding new therapeutic targets for treatment of rheumatoid arthritis.”

Current treatments for RA involve a combination of immunosuppressive drugs, which can have a serious impact on quality of life, the University of Birmingham said. By targeting PDPN-expressing cells, future treatments could be more effective and also more manageable for patients.