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

Abstract

The objective of the study was to assess the pathogenic and treatment relevance of Platelet Activating factor (PAF) in chronic spontaneous urticaria (CSU). The expression and cellular location of PAF receptor (PAFR) and serum levels of PAF and PAF acetylhydrolase (PAF-AH) in patients with moderate/severe CSU (n=45) and healthy controls (HCs, n=17) were studied. Skin samples from the active wheal (LS-CSU, 13 samples for qPCR and 33 for immunohistochemistry) and non-lesional skin (NLS-CSU, 13 samples) of CSU patients and HCs (13 samples and 5 for immunohistochemistry) were analyzed. Serum PAF and PAF-AH levels were measured by ELISA and compared between HC (10 samples) and CSU patients (25 samples) and, among them, between those refractory and non-refractory to second-generation H1 -antihistamines (sgAH). 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, whereas it was broadly 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 showed 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 sgAH non-responders versus responders (6.1 vs. 12.6; p=0.049). Our study confirms that PAF is a mediator of wheal pathogenesis in CSU. The significantly lower PAF-AH/PAF ratio in sgAH non-responders vs responders suggests that PAF could be a potential biomarker of sgAH refractoriness.