Transition from psoriasis to psoriatic arthritis is characterized by distinct alterations in peripheral blood Tc17, Th17 and CD4+ TEM cells.

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 CASPAR criteria. 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 (TEM) cells, T helper 17 (Th17) and T cytotoxic 17 (Tc17) cells differed between 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 foremost novel potential therapeutic target for the prevention of transition.