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THU0032 Predicting the Evolution of Inflammatory Arthritis in ACPA-Positive Individuals: can T-Cell Subset Help?
  1. L. Hunt1,
  2. J. L. Nam1,
  3. C. Rakieh1,
  4. P. Emery1,
  5. F. Ponchel1
  1. 1Division of Rheumatic and Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds, and the NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospital NHS Trust, Leeds, United Kingdom

Abstract

Background ACPA+ individuals with non specific musculoskeletal symptoms are at high risk of developing rheumatoid arthritis (RA). We previously demonstrated dys-regulation of T-cell subsets with loss of naïve and regulatory T-cell (Treg) in early disease.

Objectives The aim of the current study is to demonstrate the biomarker value of T-cell subset analysis for the prediction of symptom onset in ACPA+ individuals.

This preliminary data aims to highlight the clinical application of T-cell subset analysis within a predictive model for rheumatoid arthritis.

Methods 64 ACPA+ individuals without clinical synovitis at recruitment were followed in the rheumatology clinic for up to 52 months. At baseline T-cell subset analysis was performed using 6 colour flowcytometry for naïve T-cell (CD4+CD45RB+CD45RA+CD62L+), Treg (CD4+CD25highFoxp3+CD127low) and inflammation related cells (IRC: CD4+CD45RB+CD45RA+CD62L-). Analysis of 75 healthy controls (HC) enabled a reference group.

Results 33/64 (51.5%) patients developed clinical synovitis within a median follow-up of 6.1 months (range 1 week to 49 months). Of these 5 were diagnosed as undifferentiated arthritis (UA) and 28 meet the ACR/EULAR 2010 criteria for RA. Within those patients who progressed to synovitis T-cell subset analysis revealed disturbance from health in all 3 subsets. Both naïve T-cell frequency (p=0.003) and regulatory T-cell (p<0.0001) were reduced, while inflammation related cells (IRC, p=0.017) frequencies were increased. Groups however were not aged matched. Progression towards synovitis was associated with lower naïve (p=0.005) and Treg (p=0.004) frequency but increased IRC (p<0.0001). To develop a predictive model, naïve cells were coded (normal or reduced) according to the age-adjusted 95% CI of data obtained from the 75 HCs, and Treg / IRC using the 95%CI of the HC distribution as not related to age. Progression was associated with reduced naïve T-cells (p=0.009), reduced Treg (p=0.022) and increased IRC (p=0.001). Regression using these 3 parameters confirmed IRC (p=0.001) and naïve cells (p=0.011) as independent predictors of progression but Treg were less predictive as most patients showed clear reduction compared to HC95%CI (p=0.097).

Conclusions T-cell dys-regulation in ACPA+ individuals with non-specific musculoskeletal pain may be useful in predicting progression to inflammatory arthritis.

Disclosure of Interest L. Hunt: None Declared, J. Nam: None Declared, C. Rakieh: None Declared, P. Emery Consultant for: Abbott, BMS, Chugai, MSD, Pfizer, Roche, UCB., F. Ponchel: None Declared

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