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

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.

Circulating microRNA profiling is altered in the acute respiratory distress syndrome related to SARS-CoV-2 infection.

One of the hallmarks of SARS-CoV-2 infection is an induced immune dysregulation, in some cases resulting in cytokine storm syndrome and acute respiratory distress syndrome (ARDS). Several physiological parameters are altered as a result of infection and cytokine storm. Among them, microRNAs (miRNAs) might reflect this poor condition since they play a significant role in immune cellular performance including inflammatory responses. Circulating miRNAs in patients who underwent ARDS and needed mechanical ventilation (MV+; n = 15) were analyzed by next generation sequencing in comparison with patients who had COVID-19 poor symptoms but without intensive care unit requirement (MV-; n = 13). A comprehensive in silico analysis by integration with public gene expression dataset and pathway enrichment was performed. Whole miRNA sequencing identified 170 differentially expressed miRNAs between patient groups. After the validation step by qPCR in an independent sample set (MV+ = 10 vs. MV- = 10), the miR-369-3p was found significantly decreased in MV+ patients (Fold change - 2.7). After integrating with gene expression results from COVID-19 patients, the most significant GO enriched pathways were acute inflammatory response, regulation of transmembrane receptor protein Ser/Thr, fat cell differentiation, and regulation of biomineralization and ossification. In conclusion, miR-369-3p was altered in patients with mechanical ventilation requirement in comparison with COVID-19 patients without this requirement. This miRNA is involved in inflammatory response which it can be considered as a prognosis factor for ARDS in COVID-19 patients.