Novel biomarkers for early targeted and individualized treatment in Juvenile Idiopathic Arthritis.

Abstract

Background:The programmed cell death protein-1 (PD-1) and its ligands (PD-L 1 and 2) suppress immune responses, thus promoting self-tolerance. Among the immunomodulatory cells, acting through the PD-1 pathway, are the B-regulatory cells (Bregs). The role of the PD-1 pathway in Juvenile Idiopathic Arthritis (JIA) has not been adequately studied.Aims of the study:To investigate the immunophenotypic profile of T- and B-cells and the activity of the PD-1 pathway in JIA patients. More specifically, we will examine the levels of: a) the soluble form of PD-1 (sPD-1), b) Bregs; and the expression levels of: c) PD-1 on CD4+ and CD8+ T-cells, d) PD-L1 on Bregs and CD19+ B-cells, in blood and synovial fluid samples, at various stages of the disease (onset, relapse, remission, on or off treatment). The above biomarkers will be investigated for correlation with JIA activity.Methods:A case-control study of JIA patients (expected number: 60) and healthy controls (n: 20). Total expected number of samples: 100 of peripheral blood, 120 of serum (solely for soluble markers) and 60 of synovial fluid. The patients’ demographic data and treatment will be recorded. JIA will be classified according to the ILAR and the recently proposed PReS/PRINTO criteria. JIA activity will be assessed using the JADAS-10 tool. The biomarkers will be determined using multiparametric-polychromatic flow cytometry (quintuple fluorescence protocol) and immunoenzymatic assay ELISA.Anticipated benefits:Further elucidation of the immunophenotypic expression and variation of the abovementioned molecules and cells during active inflammation and remission in JIA. Thereby, the present study is expected to contribute to: a) the modern research and understanding of the confirmed immune dysfunction at the cellular level, which leads to the development of serious autoimmune diseases in childhood, such as JIA, and b) the search for biomarkers that could be targets of early “intelligent” treatment and thereby could support the implementation of precision-medicine. The early diagnosis and targeted treatment of JIA are crucial for the maintenance of normal physical functioning and the psychosocial balance of the still growing adolescent/child.