A Distinct Immature Low-Density Neutrophil Population Characterizes Acute Generalized Pustular Psoriasis

Generalized pustular psoriasis (GPP) is a severe disease featured by neutrophilic pustules and enhanced IL-36 inflammatory pathway in the skin ( Hoegler et al., 2018 Hoegler K.M. John A.M. Handler M.Z. Schwartz R.A. Generalized pustular psoriasis: a review and update on treatment. J Eur Acad Dermatol Venereol. 2018; 32: 1645-1651 Crossref PubMed Scopus (97) Google Scholar ). PBMCs reflecting the systemic inflammatory activation can provide pathogenetically relevant information ( Swindell et al., 2016 Swindell W.R. Sarkar M.K. Liang Y. Xing X. Gudjonsson J.E. Cross-disease transcriptomics: unique IL-17A signaling in psoriasis lesions and an autoimmune PBMC signature. J Invest Dermatol. 2016; 136: 1820-1830 Abstract Full Text Full Text PDF PubMed Scopus (45) Google Scholar ). Recently, a transcriptomic analysis of PBMCs and neutrophils in patients with GPP has been performed in a stable disease state ( Haskamp et al., 2021 Haskamp S. Frey B. Becker I. Schulz-Kuhnt A. Atreya I. Berking C. et al. Transcriptomes of MPO-deficient patients with generalized pustular psoriasis reveals expansion of CD4+ cytotoxic T cells and an involvement of the complement system [e-pub ahead of print]. J Invest Dermatol. 2021; (accessed 6 January 2022)https://doi.org/10.1016/j.jid.2021.12.021 Abstract Full Text Full Text PDF Scopus (5) Google Scholar ). However, transcriptomic profiling of PBMCs during an acute flare of GPP is unclear. In this study, we reported a predominant neutrophil signature in GPP PBMC and a marked increase in CD66+CD16+ low-density neutrophils (LDNs) in acute patients with GPP. Transcriptomic and functional analysis of LDNs revealed a hypoinflammatory phenotype yet enhanced release of neutrophil granule proteases, implicating that LDNs might contribute to the IL-36‒mediated inflammation in patients with GPP. A detailed description of the methods and patients’ information is presented (Supplementary Materials and Methods and Supplementary Table S1). The study was reviewed and approved by the Ethics Committee of Shanghai Skin Disease Hospital of Tongji University (Shanghai, China). The participants provided their written informed consent to participate in this study.