Circulating Immune Landscape Profiling in Psoriasis Vulgaris and Psoriatic Arthritis by Mass Cytometry

Abstract

Background. Psoriasis, a systemic disorder mediated by the immune system, can appear on the skin, joints, or both. Individuals with cutaneous psoriasis (PsC) have an elevated risk of developing psoriatic arthritis (PsA) during their lifetime. Despite this known association, the cellular and molecular mechanisms underlying this progression remain unclear. Methods. We performed high-dimensional, in-depth immunophenotyping of peripheral blood mononuclear cells (PBMCs) in patients with PsA and psoriasis vulgaris (PsV) by mass cytometry. Blood samples were collected before and after therapy for a longitudinal study. Then three sets of comparisons were made here: active PsA vs. active PsV, untreated PsV vs. treated PsV, and untreated PsA vs. treated PsA. Results. Marked differences were observed in multiple lymphocyte subsets of PsA related to PsV, with expansion of CD4⁺ T cells, CD16⁻ NK cells, and B cells. Notably, two critical markers, CD28 and CD127, specifically differentiated PsA from PsV. The expression levels of CD28 and CD127 on both Naïve T cells (T_N) and central memory CD4⁺ T cells (T_CM) were considerably higher in PsA than PsV. Meanwhile, after treatment, patients with PsV had higher levels of CD28^hi CD127^hi CD4⁺ T_CM cells, CD28^hi CD127^hi CD4⁺ T_N cells, and CD16⁻ NK cells. Conclusion. In the circulation of PsA patients, the T_N and CD4⁺ T_CM are characterized with more abundant CD28 and CD127, which effectively distinguished PsA from PsV. This may indicate that individuals undergoing PsV could be stratified at high risk of developing PsA based on the circulating levels of CD28 and CD127 on specific cell subsets.