Effects of Tildrakizumab on Circulating T Cells in Autoreactive Psoriatic Patients

10 Apr 20264 min read0 viewsJournal Feed

GIST

IntroductionT 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.MethodsPatients 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.ResultsTwenty 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.

Clinical Editorial

Study purpose and design

The study evaluated how tildrakizumab affects circulating T cell populations and autoreactive T cell responses in adults with moderate-to-severe psoriasis treated in routine clinical practice.
Autoantigen reactivity was measured at baseline using a stimulation index (SI) greater than 2 for LL37 and/or ADAMTSL5.
Longitudinal changes in T cell subsets were assessed by multiparametric flow cytometry during treatment.

Population and autoreactivity context

Among 38 psoriatic patients, 20 (52.6%) showed circulating autoreactive T cells to LL37 and/or ADAMTSL5 at baseline.
In contrast, 5 of 33 healthy donors (15.2%) exhibited autoreactivity to these autoantigens.
Baseline frequencies of proliferating T cells (Ki67+) within CD4+ and CD8+ compartments, as well as IL-17-producing CD4+ and CD8+ T cells, positively correlated with disease severity as measured by PASI.

Immunologic responses to autoantigen stimulation

In vitro stimulation of PBMCs with LL37 or ADAMTSL5 elicited Th17- and Th1-related cytokine production, but not Th2-related cytokines.

Treatment effects on circulating T cells

Tildrakizumab treatment significantly modulated several circulating T cell subsets, including Ki67+ CD4+, Ki67+ CD8+, Ki67+ Th17, Th17, and Ki67+ regulatory T cells (Tregs).
Autoreactivity to LL37 and ADAMTSL5 decreased markedly over the course of therapy.

Clinical correlations and subgroups

Clinical improvement correlated strongly with reductions in Ki67+ CD4+ and Ki67+ CD8+ T cell frequencies.
LL37-reactive patients tended to have a poorer clinical response at weeks 40 and 52, indicating potential subgroup differences in long-term outcomes.

Context and limitations

The study provides evidence that tildrakizumab can dampen autoreactive T cell proliferation and autoantigen-specific responses in autoreactive psoriatic patients.