Abstract
BackgroundGeneralized pustular psoriasis (GPP) is a rare, episodic, potentially life-threatening inflammatory disease. However, the pathogenesis of GPP, and universally accepted therapies for treating it, remain undefined.MethodsTo better understand the disease mechanism of GPP, we performed a transcriptome analysis to profile the gene expression of peripheral blood mononuclear cells (PBMCs) from patients enrolled at the time of diagnosis and receiving follow-up treatment for up to 6 months.ResultsRNA sequencing data revealed that gene expression in five GPP patients’ PBMCs was profoundly altered following acitretin treatment. Differentially expressed gene (DEG) analysis suggested that genes related to psoriatic inflammation, including CXCL1, CXCL8 (IL-8), S100A8, S100A9, S100A12 and LCN2, were significantly downregulated in patients in remission from GPP. Functional enrichment and annotation analysis unveiled a cluster of DEGs significantly associated with the function of leukocytes, particularly neutrophils. Pathway analysis suggested that a variety of pro-inflammatory pathways were inhibited in patients in remission. This analysis not only reaffirmed known signaling pathways in GPP pathogenesis, but also implicated novel factors and pathways, such as cell cycle regulation pathways. Furthermore, regulator network analysis provided bioinformatics-based support for upstream molecules as potential therapeutic targets such as oncostatin M.ConclusionsThis longitudinal analysis of blood transcriptomes provides the first evidence that dysregulated gene expression in peripheral blood may significantly contribute to psoriatic inflammation in GPP patients. Novel canonical pathways and biomarkers identified in the current research may provide insights to help understand GPP pathobiology and advance novel therapeutics.
Highlights
Generalized pustular psoriasis (GPP) is a rare, episodic, potentially life-threatening inflammatory disease
Patient sample collection, sequencing data and differential expression analysis Five adult patients affected with GPP were included in the current study
By comparing our data with this list, we found that Differentially expressed gene (DEG) were identified in nearly every aspect of neutrophil biology (Table 2), suggesting that neutrophils actively function in the pathogenesis of GPP
Summary
Generalized pustular psoriasis (GPP) is a rare, episodic, potentially life-threatening inflammatory disease. The pathogenesis of GPP, and universally accepted therapies for treating it, remain undefined. Generalized pustular psoriasis (GPP) is a potentially lifethreatening, multisystemic inflammatory disease characterized by sudden, repeated episodes of high-grade fever, generalized erythematous pustular rashes, and systemic upset. GPP is a difficult disease to treat. Therapies successful for treating plaque psoriasis are generally less effective for GPP. Since 2012, acitretin, cyclosporine or methotrexate have been the recommended first-line therapies for acute GPP. Acitretin has shown success in treating both generalized and localized pustular psoriasis, while it is less effective for plaque psoriasis [11]. Ozawa et al [12] demonstrated that the oral retinoid has higher effectiveness in GPP patients than methotrexate, cyclosporine, psoralen and ultraviolet A irradiation. Some GPP patients do not respond to existing treatments, creating an urgent need for novel drug targets and therapeutics
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
