Abstract
OBJECTIVE: Cellular mechanisms driving transition from psoriasis to psoriatic arthritis have remained largely elusive. Thus, we investigated changes within the peripheral blood T cell compartment associated with the transition phase. METHODS: In an observational study, 116 patients were examined and categorized into subgroups including psoriasis with at least one risk factor for transition to psoriatic arthritis, subclinical psoriatic arthritis according to EULAR taskforce recommendations from 2023, and definitive psoriatic arthritis meeting the Classification Criteria for Psoriatic Arthritis. Demographic and clinical characteristics of patient subgroups were analyzed. Deep T cell phenotyping using multicolor flow cytometry and machine-learning techniques were applied. RESULTS: Overlapping T cell endotypes were found among patients with subclinical psoriatic arthritis exhibiting the most notable divergence from the others. Frequencies of effector memory CD4(+) T cells, Th17, and Tc17 cells differed among patients with psoriasis with at least one risk factor for transition, subclinical psoriatic arthritis, and psoriatic arthritis. Transition-associated changes of Tc17 cell frequencies were confirmed by machine-learning-assisted unsupervised clustering analysis. Moreover, patients with enthesitis could be distinguished from those without, with Tc17 cells being the main distinctive feature. CONCLUSION: Transition from psoriasis to psoriatic arthritis was associated with distinct alterations of the peripheral blood T cell compartment, with Tc17 cells exhibiting the greatest discriminatory power. These findings provide insight into pathomechanisms driving disease progression during transition from psoriasis to psoriatic arthritis and identify Tc17 cells as the foremost novel potential therapeutic target for the prevention of transition.