Effect of T-cell exhaustion profiles of synovial fluid and peripheral blood from JIA patients on disease pathogenesis and prognosis

Concept

Juvenile idiopathic arthritis (JIA) is a chronic inflammatory disease that can cause severe disability and even mortality with joint swelling, sensitivity, loss of motion and synovial tissue damage. JIA is one of the most common inflammatory joint disease.

Chronicity in autoimmune diseases depends on the balance between pro-inflammatory and anti-inflammatory responses. One of the main factors in achieving this equilibrium is T-cell co-inhibitor receptors, which are highly expressed by exhausted-T-cells.

Previous studies revealed that T cells play an important and central role in the pathogenesis of especially the oligoarticular and polyarticular forms of the disease. We aim to define the role of T cell co-inhibitory receptors (co-IRs) for predicting the outcome of JIA and try to find a novel therapeutic target molecule.

Facts and figures

Project lead
MD MSc E Sag
Hacettepe University
sag.erdal@gmail.com
FOREUM research grant: €150.00
2018 - 2021

Meet the team

MD MSc E Sag
Hacettepe University
Prof S Ozen
Hacettepe University
Prof B Deleuran
Aarhus University

Objectives

  • To evaluate soluble levels and cell surface expressions of co-IRs in synovial fluid and peripheral blood of JIA patients
  • To design an ex-vivo disease model and perform functional analysis
  • To examine similarities and differences between different JIA subtypes
  • To define a prognostic biomarker among co-IRs
  • To explore novel therapeutic target molecule

Patient voice

Patient participation is very important to define the unmet needs from the patient perspective. We have a mother of systemic JIA patient as Patient/Parent Research Partner, who had valuable input in identifying the research questions and in the design of the study.

Interim results

A pilot study including 14 oligoarticular JIA patients was held in Denmark. We have designed an ex-vivo arthritis model using co-cultures of fibroblasts and PBMC/SFMCs. We suggest that LAG-3 may have a potential role at the pathogenesis and its effect on PBMCs may be a potential therapeutic target for the treatment of oligoarticular JIA. Based on this, a larger cohort of different JIA subtypes will be studied.

Abstracts EULAR 2019

OP0152 : Oligoarticular Juvenile Idiopathic Arthritis does not show signs of T-cell exhaustion, in spite of increased expression of co-inhibitory receptors