Journal Article

Effects of tildrakizumab on circulating T cells in autoreactive psoriatic patients

Facheris, Paola, Borroni, Riccardo G., Costanzo, Antonio, Favaro, Rebecca, Valenti, Mario

2026

Overview

T cell autoreactivity against the autoantigens LL37 and ADAMTSL5 contributes to inflammation in a subset of psoriatic patients. The immunological mechanisms underlying the treatment response in patients showing autoreactivity remain incompletely understood in clinical settings. This study investigated the impact of tildrakizumab on circulating immune populations and on autoantigen-specific T cell reactivity. Patients with moderate-to-severe psoriasis were enrolled and treated with tildrakizumab according to clinical practice. T cells autoreactivity to LL37 and ADAMTSL5 was assessed at baseline using a stimulation index (SI>2). Longitudinal changes in circulating T cell subsets were analyzed using multiparametric flow cytometry. Twenty of 38 psoriatic patients (52.6%) displayed circulating autoreactive T cells (SI>2) to LL37 and/or ADAMTSL5, compared with 5 of 33 healthy donors (15.2%). Baseline frequencies of Ki67 CD4 /CD8 , and IL-17 CD4 /CD8 T cell populations positively correlated with PASI. Stimulation of PBMCs with LL37 or ADAMTSL5 induced Th17- and Th1-related cytokines, but not Th2-related cytokines. During treatment, tildrakizumab significantly modulated multiple circulating T cell subsets, including Ki67 CD4 , Ki67 CD8 , Ki67 Th17, Th17, and Ki67 Tregs, and markedly reduced autoreactivity to both autoantigens. Notably, clinical improvement strongly correlated with reductions in Ki67 CD4 and Ki67 CD8 T cell frequencies. LL37-reactive patients exhibited a poorer clinical response at weeks 40 and 52. In autoreactive patients, tildrakizumab effectively modulated circulating T cell proliferation and reduced autoantigen-specific responses over time. LL37-reactive patients showed distinct long-term responses, suggesting that autoantigen-reactive subjects may represent a more treatment-challenging subgroup within the psoriatic population.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: ADAMTSL5 / Adult / Antibodies, Monoclonal, Humanized - pharmacology / Antibodies, Monoclonal, Humanized - therapeutic use / Antigens / Autoantigens / Autoantigens - immunology / Autoimmunity - drug effects / autoreactivity / Cathelicidins - immunology / CD4 antigen / CD8 antigen / Cell proliferation / Cytokines / Cytokines - metabolism / Disease / Female / Flow cytometry / Helper cells / Humans / inflammation / LL37 / Lymphocytes / Lymphocytes T / Male / Middle Aged / Monoclonal antibodies / Patients / Population / Psoriasis / Psoriasis - blood / Psoriasis - drug therapy / Psoriasis - immunology / Software / Statistical analysis / T cells / T-Lymphocyte Subsets - drug effects / T-Lymphocyte Subsets - immunology / T-Lymphocyte Subsets - metabolism / T-Lymphocytes - drug effects / T-Lymphocytes - immunology