[Role and clinical significance of PD-L1⁺ neutrophils in generalized pustular psoriasis]

Objective To characterize the distribution and functional phenotype of programmed death-ligand 1 (PD-L1) positive neutrophils in generalized pustular psoriasis (GPP) and determine their associations with disease severity and treatment response. Methods We integrated bioinformatic analyses with clinical samples to compare PD-L1 expression on neutrophils from peripheral blood and lesional skin among patients with GPP, healthy controls (HC), and psoriasis vulgaris (PV). PD-L1⁺ neutrophils were magnetically isolated from HC peripheral blood for in vitro culture, and 24 hours apoptosis was assessed by flow cytometry. The proportion of PD-L1⁺ neutrophils was quantified by flow cytometry and immunofluorescence and correlated with clinical indices -including GPPASI, high-sensitivity C-reactive protein (hsCRP), neutrophil-to-lymphocyte ratio (NLR), and relapse frequency, as well as clinical response to spesolimab. Results PD-L1 expression on neutrophils was significantly upregulated in both peripheral blood and lesional skin of patients with GPP, showing marked differences compared with HC and PV patients. PD-L1⁺ neutrophils exhibited delayed apoptosis at 24 hours and a pro-inflammatory phenotype characterized by increased release of IL-36γ-processing enzymes. PD-L1 levels correlated positively with GPPASI, hsCRP, and NLR. The proportion of lesional PD-L1⁺CD15⁺ neutrophils was positively associated with relapse frequency. Patients with higher baseline PD-L1 levels demonstrated better clinical responses to spesolimab. Conclusion PD-L1⁺ neutrophils are enriched in GPP and display delayed apoptosis and inflammatory activation. Their abundance is closely linked to disease activity, systemic inflammation, and biologic response, suggesting a role in shaping GPP immune heterogeneity. PD-L1⁺ neutrophils are merit consideration as a practical immunologic biomarker for monitoring disease activity and guiding individualized biologic therapy.