GENE REGULATION IN T CELLS FROM PSA PATIENTS DIFFERS BETWEEN PERIPHERAL BLOOD AND THE INFLAMED JOINTS: IMPLICATIONS FOR THE INTERPRETATION OF GWAS SIGNALS
Authors: Shi C et al.
Genome-wide association studies (GWAS) have contributed significantly to our pathogenetic understanding of complex diseases such as PsA. The identification of genetic variants that are either involved in protein coding or in regulatory processes may provide new insights in pathogenesis and potential new therapeutic targets.
In this study, primary cells from patients with PsA (n=48) were compared to healthy volunteers (n= 10) using functional genomic studies. CD4+ and CD8+ T cells were isolated. In 6 PsA patients, cells from synovial fluid were available.
RNA analysis of peripheral T cells from healthy controls and PsA patients revealed only subtle differences. Interestingly, T cells isolated from synovial fluid showed significant differences compared to T cells isolated from patient’s blood. CD4+ T cells showed more differentially expressed genes compared to CD8+ T cells and were enriched for genes involved in cytokine signaling and T cell proliferation.
This data reminds me of the pivotal studies of Costadino Pitzalis group studying synovial tissue in RA patients that allowed them to differentiate between distinct subtypes. Studies like this may help us to answer the question whether or not distinct phenotypes exist in PsA and whether studying these local inflammatory signatures may improve our understanding of disease and guide decision making.