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

Daria Bortolotti,Silvia Beltrami,Sabrina Rizzo,Gianluca Campo,Valentina Gentili,Marco Contoli,Edgardo Carosella,Giovanna Schiuma,Giovanni Strazzabosco,Savino Spadaro,Alberto Papi,Roberta Rizzo

doi:10.3390/v13091855

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.

Highlights

We report here for the first time the increased levels of sHLA-G and sHLA-E in plasma samples from hospitalized COVID-19 patients with respiratory failure
We have demonstrated that sHLA-G and sHLA-E levels were higher in plasma samples from COVID-19 patients than in hospitalized control patients with respiratory failure at the time of admission and healthy controls
The evaluation of the genetic background did not show any differences in the three groups in terms of allelic frequencies. sHLA-G was increased in patients with improved clinical outcomes, suggesting that the increased concentration of sHLA-G in plasma samples may be related to inflammation and might reflect a peculiar feature of COVID-19 evolution

Summary

Introduction

Human leukocyte antigen (HLA)-E and HLA-G belong to ‘non-classical’ HLA-class. Ib molecules, which includes -F and -H [1,2]. HLA-class Ia molecules (HLA-A, -B, and -C), HLA-Ib molecules display a low degree of polymorphism and different immunoregulatory properties [3]. Several results supported a correlation between HLA-E and HLA-G expression in physiological and pathological conditions [4,5]. HLA-G molecules interact with immune inhibitory receptors (ILT2, ILT4, KIR2DL4), modulating the functions of NK (Natural Killer) cells, T cells, B cells, and [6,7]

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Results

Conclusion