Increased sHLA-G Is Associated with Improved COVID-19 Outcome and Reduced Neutrophil Adhesion
Authors:
- Daria BortolottiDaria Bortolotti
- Valentina GentiliVGValentina Gentili
- Sabrina RizzoSRSabrina Rizzo
- Giovanna SchiumaGSGiovanna Schiuma
- Silvia BeltramiSBSilvia Beltrami
- Savino SpadaroSavino Spadaro
- Giovanni StrazzaboscoGSGiovanni Strazzabosco
- Gianluca CampoGCGianluca Campo
- Edgardo D. CarosellaECEdgardo D. Carosella
- Alberto PapiAPAlberto Papi
- Roberta RizzoRoberta Rizzo
- Marco ContoliMCMarco Contoli
Open Access
Abstract
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.Keywords
Funding Information
- Università degli Studi di Ferrara (Crowfounding 2021)
- Università di Ferrara (5x1000 2021)
This publication has 52 references indexed in Scilit:
- Quantitative In vitro Assay to Measure Neutrophil Adhesion to Activated Primary Human Microvascular Endothelial Cells under Static ConditionsJournal of Visualized Experiments, 2013
- Soluble Adhesion Molecules Correlate with Surface Expression in an In Vitro Model of Endothelial ActivationBasic & Clinical Pharmacology & Toxicology, 2013
- Serum Soluble HLA-E in Melanoma: A New Potential Immune-Related Marker in CancerPLOS ONE, 2011
- Angiotensin‐converting enzyme 2 (ACE2) expression and activity in human carotid atherosclerotic lesionsThe Journal of Pathology, 2008
- Getting to the site of inflammation: the leukocyte adhesion cascade updatedNature Reviews Immunology, 2007
- Spleen Tyrosine Kinase Syk Is Necessary for E-Selectin-Induced αLβ2 Integrin-Mediated Rolling on Intercellular Adhesion Molecule-1Immunity, 2007
- Expression and release of soluble HLA-E is an immunoregulatory feature of endothelial cell activationBlood, 2006
- Association of soluble HLA‐G plasma levels with HLA‐G allelesTissue Antigens, 2001
- Antigen-presenting function(s) of the non-classical HLA-E, -F and -G class I molecules: the beginning of a storyResearch in Immunology, 1996
- Kinetics and characterization of intercellular adhesion molecule-1 (ICAM-1) expression on keratinocytes in various inflammatory skin lesions and malignant cutaneous lymphomasJournal of the American Academy of Dermatology, 1989