Substantive Similarities Between Synovial Fluid and Synovial Tissue T cells in Inflammatory Arthritis Via Single-Cell RNA and T cell Receptor Sequencing.

OBJECTIVE: Synovial fluid (SF)-derived T cells are frequently studied as a proxy for investigating the synovial tissue (ST) T cell infiltrate in inflammatory arthritis. However, because ST is the primary site of inflammatory activity, there is debate as to whether SF provides a true reflection of the ST T cell population. METHODS: In this study, we used single-cell RNA sequencing paired with single-cell T cell receptor (TCR) sequencing to directly compare memory T cells from paired samples of SF and ST from six patients with inflammatory arthritis to investigate their similarity in terms of TCR repertoire and T cell subset composition. RESULTS: The TCR repertoires of SF and ST T cells were strikingly similar, particularly for CD8+ T cells. A median of 49% of the total CD8+ TCR repertoire in SF was shared with ST, compared with 20% shared with blood. Similarly, 47% of the ST CD8+ TCR repertoire was shared with SF compared to 25% with blood. Furthermore, once the effect of collagenase digestion on gene expression by ST T cells had been accounted for, the frequencies of specific CD8+ and CD4+ T cell subsets were, in general, similar in SF and ST and were distinct from blood. CONCLUSION: Our results suggest that T cells migrate and equilibrate between the SF and ST and maintain similar phenotypes in both sites. We conclude that SF is an appropriate proxy for investigating the T cell infiltrate in inflamed synovium, particularly in terms of investigating the TCR repertoire.

Synovial Tissue Sampling in Rheumatological Practice-Past Developments and Future Perspectives.

Synovial biopsies are performed in routine clinical care in order to refine diagnosis as well as within a research setting. Progress in the development of minimally invasive synovial sampling methods in the last century has accelerated and facilitated novel insights into disease pathogenesis. This review discusses the development of synovial biopsy techniques as well as examining the three currently most commonly used approaches: arthroscopic, blind needle biopsy and ultrasound guided approaches. It also highlights major research advances driven through synovial research and considers future developments.