POS0497 A STUDY ON THE IMMUNOREGULATORY ROLE OF THE PD1 PATHWAY IN JUVENILE IDIOPATHIC ARTHRITIS - PRELIMINARY RESULTS

Abstract

BackgroundThe Programmed cell Death protein-1 (PD1) pathway promotes self-tolerance, by inhibiting immune responses. The PD1 soluble form (sPD1), by antagonizing the binding of the membrane-bound PD1 with its ligands, may lead to the blocking of the pathway’s functions. Data regarding the role of the PD1 pathway in Juvenile Idiopathic Arthritis (JIA) are still limited.ObjectivesTo investigate the immunoregulatory role of the PD1 pathway in JIA patients.MethodsJIA patients and healthy controls participated in this study with peripheral blood (PB) and/or synovial fluid (SF) samples. sPD1 levels in serum and SF were determined by ELISA. The PD1 expression on T-helper (CD4+) and T-cytotoxic (CD8+) cells in PB and SF was analyzed by flow cytometry. A search for any association between the above biomarkers, as well as their relation with JIA activity was then performed. Inactive disease was defined according to Wallace criteria.Results77 Caucasian patients (52 female) participated so far in this study, with a median (range) age of 13 (2-19) years; their JIA subtypes were: oligoarthritis (33%), polyarthritis (26%), psoriatic (12%), enthesitis-related (16%), systemic (10%) and undifferentiated (3%). Ten healthy children served as controls. As compared to controls, a subpopulation of these JIA patients (n=46) had a significantly higher median percentage of PD1+CD4+ (1.15 vs. 0.32%, p=0.029) and PD1+CD8 T cells (1.34 vs. 0.4%, p=0.006) in PB. In regard to the JIA status, patients with activity (n=33) had a significantly higher median percentage of both PD1+CD4+ and PD1+CD8 T cells in PB, as compared to those with inactive disease (n=13) (1.36 vs. 0.87%, p=0.034 and 2.03 vs. 0.45%, p<0.001, respectively). Additionally, in a sample of the patients with disease activity (n=22), the median serum sPD1 level was statistically significantly higher, as compared to a sample of those with inactive JIA (n=10) (218.3 vs. 186.7pg/ml, p=0.035). In patients with concurrent serum and SF samples (n=7), the median sPD1 level was statistically significantly higher in the SF than in the serum [1104.4 vs. 773.4pg/ml, p=0.028). No correlation was though found between the sPD1 levels and the PD1 cellular surface expression (n=16 PB/serum, n=11 SF).ConclusionThese preliminary results indicated an sPD1 compartmentalization in active JIA, as sPD1 levels were more prominently raised in the inflamed joint than in the PB. Α higher number of circulating T-helper and T-cytotoxic cells expressing PD1 were also detected in active JIA. Further investigation in a larger sample of JIA patients may verify these observations and contribute to unraveling the precise role of the PD1 pathway in the pathogenesis and persistence of the joint inflammation.References[1]Leong et al. Recent advances in our understanding of the pathogenesis of juvenile idiopathic arthritis and their potential clinical implications. Expert Rev Clin Immunol. 2018 Nov;14(11):933-944.[2]Zhang et al. The PD-1/PD-L pathway in rheumatic diseases. J Formos Med Assoc. 2021 Jan;120(1 Pt 1):48-59.Disclosure of InterestsNone declared.