T cell subsets: an immunological biomarker to predict progression to clinical arthritis in ACPA-positive individuals

Abstract

ObjectivesAnticitrullinated protein antibody (ACPA)+ individuals with non-specific musculoskeletal symptoms are at risk of inflammatory arthritis (IA). This study aims to demonstrate the predictive value of T cell subset quantification for progression towards IA and compare it with previously identified clinical predictors of progression.Methods103 ACPA+ individuals without clinical synovitis were observed 3-monthly for 12 months and then as clinically indicated. The end point was the development of IA. Naïve, regulatory T cells (Treg) and inflammation related cells (IRCs) were quantified by flow cytometry. Areas under the ROC curve (AUC) were calculated. Adjusted logistic regressions and Cox proportional hazards models for time to progression to IA were constructed.ResultsCompared with healthy controls (age adjusted where appropriate), ACPA+ individuals demonstrated reduced naïve (22.1% of subjects) and Treg (35.8%) frequencies and elevated IRC (29.5%). Of the 103 subjects, 48(46.6%) progressed. Individually, T cell subsets were weakly predictive (AUC between 0.63 and 0.66), although the presence of 2 T cell abnormalities had high specificity. Three models were compared: model-1 used T cell subsets only, model-2 used previously published clinical parameters, model-3 combined clinical data and T cell data. Model-3 performed the best (AUC 0.79 (95% CI 0.70 to 0.89)) compared with model-1 (0.75 (0.65 to 0.86)) and particularly with model-2 (0.62 (0.54 to 0.76)) demonstrating the added value of T cell subsets. Time to progression differed significantly between high-risk, moderate-risk and low-risk groups from model-3 (p=0.001, median 15.4 months, 25.8 months and 63.4 months, respectively).ConclusionsT cell subset dysregulation in ACPA+ individuals predates the onset of IA, predicts the risk and faster progression to IA, with added value over previously published clinical predictors of progression.

T-cell subset abnormalities predict progression along the Inflammatory Arthritis disease continuum: implications for management

“…We established that reduced (age-normalised) frequencies of naive CD4+ T-cells in early RA at baseline were associated with failure to achieve remission with MTX treatment 22 . Furthermore, we showed that the progression towards IA from at-risk stages (ACPA + no synovitis) could be predicted using all 3 T-cell subsets 23 .…”

“…Following 2 initial reports describing the potential of T-cell subset quantification associated with 2 stages of the IA-continuum (at-risk and response to treatment) 22,23 , in this study we describe data from 705 patients recruited at distinct stages of the IA continuum, to model the potential clinical utility of scoring T-cells subset as biomarkers predictive of progression to the next stage of the continuum, with implications for targeted management. We first, modelled the clinical value of phenotyping T-cells for the prediction of progression from one stage to the next.…”

THE RELATIONSHIP OF FoxP3+ T REGULATORY CELLS TO DISEASE ACTIVITY AND ANTIBODY LEVELS IN EARLY RHEUMATOID ARTHRITIS

“…L. Hunt и соавт. [46] проанализировали риск развития РА в группе 103 АЦЦП-позитивных паци-ентов без признаков синовита. Прогрессирование забо-левания отмечалось у 46,6% больных, причем у подавля-ющего большинства -в течение первых 12 мес.…”

Problems of Rheumatoid Arthritis Immunopathology: Evolution of the Disease

“…Недавно получены данные о том, что у АЦЦП-пози-тивных людей без клинических признаков артрита наблю-дается снижение числа наивных и регуляторных Т-клеток и увеличение содержания так называемых «клеток, связан-ных с воспалением» (inflammation related cells), причем комбинация этих нарушений позволяет прогнозировать риск развития РА [123]. В других исследованиях было по-казано, что у пациентов с серопозитивной артралгией (как и при серопозитивном РА) наблюдается снижение (связа-но с апоптозом) числа естественных киллерных (ЕК) кле-ток (CD56 dim ), которые при активации посредством CD16 (FcγRIIIa) начинают синтезировать широкий спектр «про-воспалительных» цитокинов [124].…”