Low Levels of Natural Anti-α-N-Acetylgalactosamine (Tn) Antibodies Are Associated With COVID-19.

Adrien Breiman,Jacques Le Pendu,Nathalie Ruvoën-Clouet,Nicolai Bovin,Tiffany Beauvais,Nicolas Jouand,Hanane El Kenz,Marie Deleers,Nathalie Labarrière,Jézabel Rocher

doi:10.3389/fmicb.2021.641460

Abstract

Human serum contains large amounts of anti-carbohydrate antibodies, some of which may recognize epitopes on viral glycans. Here, we tested the hypothesis that such antibodies may confer protection against COVID-19 so that patients would be preferentially found among people with low amounts of specific anti-carbohydrate antibodies since individual repertoires vary considerably. After selecting glycan epitopes commonly represented in the human anti-carbohydrate antibody repertoire that may also be expressed on viral glycans, plasma levels of the corresponding antibodies were determined by ELISA in 88 SARS-CoV-2 infected individuals, including 13 asymptomatic, and in 82 non-infected controls. We observed that anti-Tn antibodies levels were significantly lower in patients as compared to non-infected individuals. This was not observed for any of the other tested carbohydrate epitopes, including anti-αGal antibodies used as a negative control since the epitope cannot be synthesized by humans. Owing to structural homologies with blood groups A and B antigens, we also observed that anti-Tn and anti-αGal antibodies levels were lower in blood group A and B, respectively. Analyses of correlations between anti-Tn and the other anti-carbohydrates tested revealed divergent patterns of correlations between patients and controls, suggesting qualitative differences in addition to the quantitative difference. Furthermore, anti-Tn levels correlated with anti-S protein levels in the patients’ group, suggesting that anti-Tn might contribute to the development of the specific antiviral response. Overall, this first analysis allows to hypothesize that natural anti-Tn antibodies might be protective against COVID-19.

Highlights

Viral envelope proteins, including those of the severe acute respiratory syndrome coronavirus 2 SARS-CoV-2 are extensively glycosylated (Watanabe et al, 2020)
It has been established that several types of enveloped viruses, including influenza virus, murine C retrovirus, porcine endogenous retrovirus, lymphocytic choriomeningitis virus, Newcastle disease virus, Sindbis virus, vesicular stomatitis virus, measles virus, and paramyxovirus present the αGal antigen when produced in cells that synthesize it (Galili, 2020)
Considering the structural relationship with the A blood group antigen, levels of anti-Tn were expected to be lower in blood group A individuals in comparison with blood group O and B and this was verified both for the control and COVID-19 groups (Figure 2)

Summary

Introduction

Viral envelope proteins, including those of the severe acute respiratory syndrome coronavirus 2 SARS-CoV-2 are extensively glycosylated (Watanabe et al, 2020) Since these glycans are synthesized by the host cell enzymatic machinery, they are part of the self and have little immunogenic potential. The αGal antigen is the most extensively studied example of a carbohydrate epitope that can lead to the elimination of viruses through natural antibodies (Galili, 2019). Anti-A antibodies could block the interaction between SARS-CoV S protein and its cellular receptor, the angiotensin-converting enzyme ACE2, when the viral protein was produced by cells expressing the A blood group antigen (Guillon et al, 2008). Coherent with the notion that natural anti-carbohydrate could have a protective effect, we recently observed that COVID-19 patients present lower levels of anti-A and/or anti-B blood group antibodies than controls (Deleers et al, 2020)

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Conclusion