Some Joints May Be Primed for Rheumatoid Arthritis Before Birth, Study Finds

Researchers at the Kennedy Institute of Rheumatology, University of Oxford, have found evidence that some joints may be more vulnerable to inflammatory arthritis before birth, a discovery that could help explain why rheumatoid arthritis repeatedly attacks certain joints while leaving others largely untouched. The study, published in Nature Immunology, suggests the answer may depend not only on the immune system but on biological differences built into individual joints during development.

The researchers compared proximal interphalangeal (PIP) finger joints, which rheumatoid arthritis frequently affects, with distal interphalangeal (DIP) joints near the fingertips, which are generally spared. Using single-cell sequencing, image analysis and high-resolution 3D X-ray scanning at the Diamond Light Source facility, they found that PIP joints already had a larger volume of synovial tissue and more PI16-positive fibroblasts, a specialized connective tissue cell, before birth.

"For decades we have known that rheumatoid arthritis selectively targets particular joints, but one of the great unanswered questions is why?" said Christopher Buckley, Kennedy Professor of Translational Rheumatology at Oxford. "Our findings suggest that the answer lies not only in the immune system but also in the tissues themselves." The PI16-positive fibroblasts, concentrated around blood vessels and where tendons and ligaments meet other tissue, also reacted differently to inflammatory signals than other fibroblast populations.

The research was led by the Kennedy Institute with colleagues at the University of Birmingham, University College London and Diamond Light Source, and was supported by the Medical Research Council. "PI16-positive fibroblasts were enriched in vulnerable joints and responded differently to inflammatory signals," said Dr. Sarah Davidson, a postdoctoral researcher at the Kennedy Institute and one of the study's first authors.