Increased sHLA-G Is Associated with Improved COVID-19 Outcome and Reduced Neutrophil Adhesion

• Main Authors: Daria Bortolotti, Valentina Gentili, Sabrina Rizzo, Giovanna Schiuma, Silvia Beltrami, Savino Spadaro, Giovanni Strazzabosco, Gianluca Campo, Edgardo D. Carosella, Alberto Papi, Roberta Rizzo, Marco Contoli
• Format: Article
• Language: English
• Published: MDPI AG 2021-09-01
• Series: Viruses
• Subjects: HLA-G; COVID-19; E-selectin; ICAM-1; CD160; neutrophil
• Online Access: https://www.mdpi.com/1999-4915/13/9/1855

Human leukocyte antigen (HLA) is a group of molecules involved in inflammatory and infective responses. We evaluated blood sHLA-E and sHLA-G levels in hospitalized COVID-19 patients with respiratory failure and their relationship with clinical evolution, changes in endothelial activation biomarker profile, and neutrophil adhesion. sHLA-E, sHLA-G, and endothelial activation biomarkers were quantified by ELISA assay in plasma samples. Neutrophil adhesion to endothelium was assessed in the presence/absence of patients’ plasma samples. At admission, plasma levels of sHLA-G and sHLA-E were significantly higher in COVID-19 patients with respiratory failure compared to controls. COVID-19 clinical improvement was associated with increased sHLA-G plasma levels. In COVID-19, but not in control patients, an inverse correlation was found between serum sICAM-1 and E-selectin levels and plasma sHLA-G values. The in vitro analysis of activated endothelial cells confirmed the ability of HLA-G molecules to control sICAM-1 and sE-selectin expression via CD160 interaction and FGF2 induction and consequently neutrophil adhesion. We suggest a potential role for sHLA-G in improving COVID-19 patients’ clinical condition related to the control of neutrophil adhesion to activated endothelium.