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

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-?Gal 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-?Gal 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.

SUBMITTER: Breiman A

PROVIDER: S-EPMC7905038 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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

Breiman Adrien A Ruvoën-Clouet Nathalie N Deleers Marie M Beauvais Tiffany T Jouand Nicolas N Rocher Jézabel J Bovin Nicolai N Labarrière Nathalie N El Kenz Hanane H Le Pendu Jacques J

Frontiers in microbiology 20210211

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 ...[more]

PMID: 33643275

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Project description:While native blood group A-like glycans have not been demonstrated in prokaryotic microorganisms as a source of human "natural" anti-A isoagglutinin production, and metazoan eukaryotic N-acetylgalactosamine O-glycosylation of serine or threonine residues (O-GalNAc-Ser/Thr-R) does not occur in bacteria, the O-GalNAc glycan-bearing ovarian glycolipids, discovered in C57BL/10 mice, are complementary to the syngeneic anti-A-reactive immunoglobulin M (IgM), which is not present in animals that have undergone ovariectomy prior to the onset of puberty. These mammalian ovarian glycolipids are complementary also to the anti-A/Tn cross-reactive Helix pomatia agglutinin (HPA), a molluscan defense protein, emerging from the coat proteins of fertilized eggs and reflecting the snail-intrinsic, reversible O-GalNAc glycosylations. The hexameric structure of this primitive invertebrate defense protein gives rise to speculation regarding an evolutionary relationship to the mammalian nonimmune, anti-A-reactive immunoglobulin M (IgM) molecule. Hypothetically, this molecule obtains its complementarity from the first step of protein glycosylations, initiated by GalNAc via reversible O-linkages to peptides displaying Ser/Thr motifs, whereas the subsequent transferase depletion completes germ cell maturation and cell renewal, associated with loss of glycosidic bonds and release of O-glycan-depleted proteins, such as complementary IgM revealing the structure of the volatilely expressed "lost" glycan carrier through germline Ser residues. Consequently, the evolutionary/developmental first glycosylations of proteins appear metabolically related or identical to that of the mucin-type, potentially "aberrant" monosaccharide GalNAcα1-O-Ser/Thr-R, also referred to as the Tn (T "nouvelle") antigen, and explain the anti-Tn cross-reactivity of human innate or "natural" anti-A-specific isoagglutinin and the pronounced occurrence of cross-reactive anti-Tn antibody in plasma from humans with histo-blood group O. In fact, A-allelic, phenotype-specific GalNAc glycosylation of plasma proteins does not occur in human blood group O, affecting anti-Tn antibody levels, which may function as a growth regulator that contributes to a potential survival advantage of this group in the overall risk of developing cancer when compared with non-O blood groups.

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

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

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

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Low Levels of Natural Anti-α-&lt;i&gt;N&lt;/i&gt;-Acetylgalactosamine (Tn) Antibodies Are Associated With COVID-19.

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