PMID- 34578436 OWN - NLM STAT- MEDLINE DCOM- 20211014 LR - 20211014 IS - 1999-4915 (Electronic) IS - 1999-4915 (Linking) VI - 13 IP - 9 DP - 2021 Sep 17 TI - Increased sHLA-G Is Associated with Improved COVID-19 Outcome and Reduced Neutrophil Adhesion. LID - 10.3390/v13091855 [doi] LID - 1855 AB - 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. FAU - Bortolotti, Daria AU - Bortolotti D AUID- ORCID: 0000-0003-4496-9561 AD - Department of Chemical, Pharmaceutical and Agricultural Science, University of Ferrara, 44121 Ferrara, Italy. FAU - Gentili, Valentina AU - Gentili V AUID- ORCID: 0000-0003-4572-5497 AD - Department of Chemical, Pharmaceutical and Agricultural Science, University of Ferrara, 44121 Ferrara, Italy. FAU - Rizzo, Sabrina AU - Rizzo S AD - Department of Chemical, Pharmaceutical and Agricultural Science, University of Ferrara, 44121 Ferrara, Italy. FAU - Schiuma, Giovanna AU - Schiuma G AUID- ORCID: 0000-0003-4652-5550 AD - Department of Chemical, Pharmaceutical and Agricultural Science, University of Ferrara, 44121 Ferrara, Italy. FAU - Beltrami, Silvia AU - Beltrami S AUID- ORCID: 0000-0002-5923-9265 AD - Department of Chemical, Pharmaceutical and Agricultural Science, University of Ferrara, 44121 Ferrara, Italy. FAU - Spadaro, Savino AU - Spadaro S AUID- ORCID: 0000-0001-5027-5318 AD - Intensive Care Unit, Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy. FAU - Strazzabosco, Giovanni AU - Strazzabosco G AD - Department of Chemical, Pharmaceutical and Agricultural Science, University of Ferrara, 44121 Ferrara, Italy. FAU - Campo, Gianluca AU - Campo G AD - Cardiology Unit, Azienda Ospedaliero Universitaria di Ferrara, Cona, 44124 Ferrara, Italy. FAU - Carosella, Edgardo D AU - Carosella ED AD - CEA, Institute of Emerging Diseases and Innovative Therapies (iMETI), Research Division in Hematology and Immunology (SRHI), Saint-Louis Hospital, 75001 Paris, France. FAU - Papi, Alberto AU - Papi A AD - Respiratory Section, Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy. AD - Respiratory Unit, Azienda Ospedaliera Universitaria Ferrara, Cona, 44124 Ferrara, Italy. FAU - Rizzo, Roberta AU - Rizzo R AUID- ORCID: 0000-0001-9507-9126 AD - Department of Chemical, Pharmaceutical and Agricultural Science, University of Ferrara, 44121 Ferrara, Italy. AD - Industrial Research and Technology Transfer Laboratory (LTTA), University of Ferrara, 44121 Ferrara, Italy. FAU - Contoli, Marco AU - Contoli M AUID- ORCID: 0000-0002-2731-5809 AD - Respiratory Section, Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy. AD - Respiratory Unit, Azienda Ospedaliera Universitaria Ferrara, Cona, 44124 Ferrara, Italy. LA - eng GR - Crowfounding 2021/Universita degli Studi di Ferrara/ GR - 5x1000 2021/Universita di Ferrara/ PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210917 PL - Switzerland TA - Viruses JT - Viruses JID - 101509722 RN - 0 (Biomarkers) RN - 0 (HLA-G Antigens) SB - IM MH - Aged MH - Alleles MH - *Biomarkers MH - COVID-19/epidemiology/*immunology/*virology MH - Cell Adhesion/immunology MH - Endothelial Cells/immunology/metabolism MH - Enzyme-Linked Immunosorbent Assay MH - Female MH - Gene Frequency MH - HLA-G Antigens/blood/*immunology MH - Humans MH - Male MH - Middle Aged MH - Models, Biological MH - Neutrophils/*immunology/metabolism MH - SARS-CoV-2/*immunology PMC - PMC8473385 OTO - NOTNLM OT - CD160 OT - COVID-19 OT - E-selectin OT - HLA-G OT - ICAM-1 OT - neutrophil COIS- The authors declare no conflict of interest. EDAT- 2021/09/29 06:00 MHDA- 2021/10/15 06:00 PMCR- 2021/09/17 CRDT- 2021/09/28 01:26 PHST- 2021/08/13 00:00 [received] PHST- 2021/09/12 00:00 [revised] PHST- 2021/09/14 00:00 [accepted] PHST- 2021/09/28 01:26 [entrez] PHST- 2021/09/29 06:00 [pubmed] PHST- 2021/10/15 06:00 [medline] PHST- 2021/09/17 00:00 [pmc-release] AID - v13091855 [pii] AID - viruses-13-01855 [pii] AID - 10.3390/v13091855 [doi] PST - epublish SO - Viruses. 2021 Sep 17;13(9):1855. doi: 10.3390/v13091855.