Baseline Th17/Tc17 and LAG-3 levels serve as candidate exploratory markers for early ixekizumab response in psoriasis

Introduction Psoriasis is a T cell-mediated inflammatory skin disease, and biologics have demonstrated promising efficacy. However, some patients remain dissatisfied with early therapeutic outcomes. Immune checkpoint molecules on T cells play critical roles in psoriasis pathogenesis, yet their impact on therapeutic response remains unclear. This study aimed to identify predictive markers for the early therapeutic efficacy of ixekizumab in psoriasis patients. Methods Twenty-two patients with plaque psoriasis were enrolled in this study. All participants received ixekizumab for 24 weeks. Peripheral blood was collected at multiple time points, and flow cytometry was used to assess T cell subsets and the expression of immune checkpoint molecules, including T cell immunoreceptor with Ig and ITIM domains (TIGIT), lymphocyte activating gene 3 (LAG-3), cytotoxic T-lymphocyte associated protein 4 (CTLA-4), B and T lymphocyte-associated protein, endothelial protein C receptor (PROCR), podoplanin (PDPN), programmed cell death 1 (PD-1), and B7-Homolog 6 (B7-H6). Results Ixekizumab treatment reduced the proportion of T helper 17 (Th17) cells and IL-17-secreting CD8 + T (Tc17) cells and downregulated B7-H6 and LAG-3 expression on CD4 + T cells by week 24. Similarly, LAG-3 expression on CD8 + T cells decreased. Notably, baseline levels of Th17 and Tc17 cells, as well as LAG-3 expression on CD4 + and CD8 + T cells, were higher in non-early responders than in early responders. Conclusion Ixekizumab treatment may restore immune dysregulation in psoriasis patients. Baseline proportions of Th17 and Tc17 cells, along with LAG-3 expression on CD4 + and CD8 + T cells, may serve as candidate exploratory markers for the early therapeutic efficacy of ixekizumab.