Generalized pustular psoriasis (GPP) is a severe psoriatic subtype characterized by epidermal neutrophil infiltration. How disease-contributing variants in IL36RN and MPO promote inflammation in immune cells is unknown. We assessed transcriptomes of MPO-deficient patients using single cell RNA-sequencing (scRNAseq) of peripheral blood mononuclear cells (PBMCs) and RNA-sequencing of neutrophils in stable and acute state. Cell type annotation by multimodal reference mapping of scRNAseq data was verified by flow cytometry; proportions of CD4+ cytotoxic T-lymphocytes (CTLs) and CD8+ effector memory T-cells (TEMs) were increased in GPP. The expression of a marker for CD4+CTLs was elevated in GPP patients with disease-contributing variants compared to non-carriers (p=0.0015). Differentially expressed genes (DEGs) involved in complement system were enriched in patients’ neutrophils. In acute state, altered proportions of CD8+TEMs and monocytes were observed. Predictions of receptor-ligand networks showed an involvement of multiple PBMCs and a decline of cell type-specific interactions upon episode’s clearance. Pathway analysis of DEGs in neutrophils pointed to interferon type I signaling. Future studies assessing these cells/ pathways will show their contribution to GPP’s pathogenesis and the role of agents depleting or inactivating CD4+CTLs as potential therapeutics.

ESDR230 - Transcriptomes of MPO-deficient patients with generalized pustular psoriasis reveals expansion of CD4+ cytotoxic T cells and an involvement of complement system and interferon pathways

50th Annual Meeting of the European Society for Dermatological Research. VIRTUAL MEETING