Th124 - Regulatory T Cell Fitness as Biomarker for Disease Activity in Juvenile Idiopathic Arthritis

Meryl Attrill – Division of Infection and immunity – UCL - Institute of Immunity and Transplantation; Diana Shinko, PhD – Division of Infection and immunity – UCL - Institute of Immunity and Transplantation; Telma Martins Viveiros – Division of Infection and immunity – UCL - Institute of Immunity and Transplantation; Nina de Gruijter – Division of Medicine – Centre for Adolescent Rheumatology Versus Arthritis at UCL UCLH and GOSH, Centre for Rheumatology Research, UCL; Bethany Jebson – UCL Great Ormond Street Institute of Child Health, Centre for Adolescent Rheumatology Versus Arthritis at UCL UCLH and GOSH, NIHR Biomedical Research Centre at GOSH; Vicky Alexiou – UCL Great Ormond Street Institute of Child Health, Centre for Adolescent Rheumatology Versus Arthritis at UCL UCLH and GOSH; Melissa Kartawinata – UCL Great Ormond Street Institute of Child Health, Centre for Adolescent Rheumatology Versus Arthritis at UCL UCLH and GOSH; Lucy Wedderburn – UCL Great Ormond Street Institute of Child Health, Centre for Adolescent Rheumatology Versus Arthritis at UCL UCLH and GOSH, NIHR Biomedical Research Centre at GOSH; Elizabeth Rosser, PhD – Division of Medicine – Centre for Adolescent Rheumatology Versus Arthritis at UCL UCLH and GOSH, Centre for Rheumatology Research, UCL; studies CHARMS & JIAP – UCL Great Ormond Street Institute of Child Health, Centre for Adolescent Rheumatology Versus Arthritis at UCL UCLH and GOSH, NIHR Biomedical Research Centre at GOSH

Abstract Text: Juvenile Idiopathic Arthritis (JIA) affects about 1 in 1000 children worldwide. The majority of cases are oligoarticular and rheumatoid factor negative (RF-) polyarticular JIA, characterised by repeated flares of joint inflammation without skin/systemic involvement leading to pain, fatigue, and ultimately joint destruction and disability. However, no reliable biomarker exists to predict the erratic disease course. In JIA the immunoregulatory balance is broken with altered regulatory T cells (Tregs). Thus, monitoring changes in Tregs could offer novel biomarker potential of subclinical disease activity.
Utilising full-spectrum flow cytometry and unbiased analysis, we identified three Treg clusters increased in peripheral blood (PB) Tregs from clinically active JIA patients (active joint count, AJC ≥1), including CD226highCD25low effector-like Tregs, while a 4-1BBlowID2intermediate Treg cluster predominated in inactive JIA (AJC=0). The ratio of these Treg clusters correlated to clinical Juvenile Arthritis disease activity score (cJADAS) and predicted inactive individuals that flared by 6-month follow-up.
Moreover, machine learning biomarker discovery on nanoString Treg gene signature plus data from sorted Tregs (CD4+CD25hiCD127low) could successfully differentiate active JIA Tregs from healthy control (HC) Tregs (AUC=0.9875). Biomarker scores of Tregs from clinically inactive individuals (cJADAS < 0.5) were significantly different (p=0.011) from samples with higher cJADAS (≥0.5), but not different from HC Tregs.
Thus, our data indicates altered Treg fitness as an important factor for disease progression versus remission. Validation of these PB Treg-derived biomarkers could lead to more personalised disease management, for example starting preventative treatment if a flare is likely or withdrawing medication safely when sustained remission is indicated.