Oxford researchers examine why some joints may be more vulnerable to rheumatoid arthritis
Scientists at the Kennedy Institute of Rheumatology at the University of Oxford in the United Kingdom have found that some joints may be more prone to inflammation in rheumatoid arthritis even before birth. ScienceDaily reports. The findings may help explain why the disease often affects certain joints while others largely remain unaffected.
The study, “Embryonic origins of site-specific arthritis,” was published in the journal Nature Immunology. Rheumatoid arthritis is an autoimmune disease in which the immune system attacks the synovial membrane of the joints. This can cause pain, swelling and stiffness and, over time, damage to cartilage, bones and surrounding tissues.
Finger joints compared
The researchers compared proximal interphalangeal joints, or PIP joints, which are often affected by rheumatoid arthritis, with distal interphalangeal joints near the fingertips — DIP joints, which usually remain unaffected. PIP joints were found to have a larger volume of synovial tissue and more PI16-positive fibroblasts, specialized connective tissue cells.
These differences were already present during prenatal development. According to the authors, the local tissue environment of a joint may influence whether inflammation can later develop there.
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Differences in fibroblasts
The team used single-cell sequencing, image analysis and high-resolution three-dimensional X-ray scanning to create a detailed map of the development of human finger joints. In developing joints, structural rather than immune cells predominated, including fibroblasts and cells responsible for cartilage formation.
PI16-positive fibroblasts were more prevalent in PIP joints. They were concentrated near blood vessels and at sites where tendons and ligaments connect to adjacent tissues. These cells also responded differently to inflammatory signals than other fibroblast populations: alongside an overall pro-inflammatory response, they showed changes in biological pathways related to immune regulation and tissue organization.
The study was conducted by scientists from the University of Oxford together with colleagues from the University of Birmingham, University College London and Diamond Light Source. The work was supported by the UK Medical Research Council.
