New transcriptome and clinical findings of platelet-activating factor in chronic spontaneous urticaria: Pathogenic and treatment relevance

Urticaria is characterized by transient wheal-and-flare skin reaction with pruritus. More than 5 million people suffer from persisting urticaria symptoms in Europe, causing a huge burden on patients and healthcare systems. The aim of this study was to evaluate the relevance of Platelet Activating factor (PAF) in chronic spontaneous urticaria (CSU).

Skin samples of 45 patients with moderate/severe CSU and 17 healthy controls were analyzed for the expression and cellular location of PAF receptor (PAFR) and serum levels of PAF and PAF acetylhydrolase (PAF-AH). Serum PAF and PAF-AH levels were assessed by ELISA and compared between patient and healthy controls and also between those refractory and non-refractory to 2nd-generation H1-antihistamines. PAFR mRNA expression was significantly higher in LS-CSU versus HCs (p = 0.014). PAFR positive staining in immunohistochemistry was mainly found in the epidermal basal layer in HCs, while it was largely present along the epidermis in LS-CSU samples. Endothelial cells showed PAFR expression exclusively in LS-CSU and NLS-CSU samples. PAFR expression was observed in the nerves of HC, LS-CSU, and NLS-CSU samples. Double PAFR/CD43 expression demonstrated that T-lymphocytes were the main cell type from the wheal inflammatory infiltrate expressing PAFR. A significantly lower PAF-AH/PAF ratio was observed in 2nd-generation H1-antihistamines non-responders versus responders (6.1 vs. 12.6; p = 0.049).

In conclusion, this study corroborates that PAF is a mediator of wheal pathogenesis in CSU and suggests that PAF could be a potential biomarker of 2nd-generation H1-antihistamines refractoriness due to the significantly lower PAF-AH/PAF ratio in 2nd-generation H1-antihistamines non-responders vs responders.