A Study on the Immunoregulatory Role of the PD1 Pathway in Juvenile Idiopathic Arthritis

Objectives: To investigate the immunoregulatory role of the Programmed-cell-Death-protein-1 (PD1) pathway, an inhibitory immune checkpoint, in Juvenile Idiopathic Arthritis (JIA).Methods: The PD1 expression on CD4+ and CD8+ T-cells was determined by flow cytometry and the PD1 soluble form (sPD1) levels by ELISA, in peripheral blood (PB)/serum and synovial fluid (SF) samples of JIA patients and healthy controls (HCs).We searched for any association in-between the biomarkers and with JIA activity.Results: 101 Caucasian patients (69 female), aged 12 (8-15) years, and 20 HCs participated in this study.The PB PD1 expression on T-cells was higher in: a. JIA patients vs HCs (CD4: 1.24% vs 0.32%, p=0.007,CD8: 1.6% vs 0.4%, p=0.002).b. active vs inactive JIA (CD4: 1.44% vs 0.87%, p=0.072,CD8: 2.1% vs 0.93%, p=0.005).The SF PD1 expression on T-cells correlated strongly and positively with the disease activity (CD4: ρ=0.55, p=0.022,CD8: ρ=0.555, p=0.026).The SF PD1 expression on CD8 T-cells was higher in patients on-treatment vs those offtreatment (21.3% vs 5.83% p=0.004).The sPD1 levels were higher in the SF vs the serum (801pg/ml vs 367.2, p=0.013), without an association with disease activity.Conclusion: These results indicate an up-regulation of the PD1-pathway in JIA, at least quantitatively, especially in active disease.sPD1 is compartmentally produced at the inflamed joints.Further investigation in a larger sample of JIA patients may verify these observations and contribute to unravelling the precise role of the PD1 pathway in the pathogenesis and persistence of the joint inflammation.