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The T cell receptor β chain (TCRβ) repertoire in the synovial tissue of patients with rheumatoid arthritis (RA) has a high degree of similarity between different joints and between different locations in the same joint, according to new research.

Previous studies have produced conflicting results as to whether the same T cell clones drive inflammation in different joints. To address this question, the authors of the present study used next generation sequencing to analyse the entire TCRβ repertoire of T cells from synovial tissue, synovial fluid and peripheral blood of patients with RA.

“With the advent of novel sequencing technologies, we were able to study the full repertoire of TCRβ clones quantitatively and with unprecedented detail and accuracy in a larger group of patients than had previously been possible, comparing synovial tissues within and between joints,” says corresponding author Niek de Vries. “The results indicate that shared T cell responses are indeed responsible for the inflammation in different joints.”

The researchers compared the overlap between the top 25 most expanded TCRβ clones at different sites in the same joint and in different inflamed joints in the same patient, and found an overlap of ~50% in both instances. This high degree of similarity suggests that inflammation is driven by a limited number of clones. “These observations are good news since they support the feasibility of immunotherapies that selectively target dominant T cell responses,” states de Vries.

Interestingly, the TCRβ repertoires of synovial tissue and synovial fluid from the same joint shared only a low degree of similarity. “This result indicates that for the study of lymphocyte specificity, synovial tissue and synovial fluid are not interchangeable,” explains de Vries.

TCRβ repertoires of synovial tissue and synovial fluid from the same joint shared only a low degree of similarity

Restricting such studies to use synovial tissue alone will inevitably increase demand for a scarce resource that is normally collected by arthroscopy-guided biopsy. However, the high degree of similarity in the TCRβ repertoire at different synovial tissue locations in the same joint suggests that synovial tissue could potentially be gathered using a less targeted and less time-consuming technique, thereby increasing the supply of tissue for research.