March 8-14 2021
Severely ill patients may be lacking in a particular sugar
Antibodies are important weapons in the organism’s protective armoury against pathogens. They are made up of 2 domains: the Fc portion, recognised by the immune effector cells (lymphocytes for example) and the Fab portion, which recognizes the antigen. It is important to note the presence of a glycan (sugar), at position 297 in the Fc domain, and, more precisely, a fucose residue that plays an essential role in antibody functioning.
Some antibodies are not fucosylated, in other words, the glycan chain does not contain the fucose residue. We find these antibodies in allo-immune responses (against nonself blood cells) and against enveloped viruses. These non-fucosylated antibodies trigger a strong cytotoxic response (ADCC, standing for “antibody-dependent cell-mediated cytotoxicity”). This is how they are used in the treatment of some cancers to target the tumours. Dutch researchers have recently shown that they may be present in serious cases of COVID-19 and reinforce the cytokinetic storm causing pathogenesis.
This can be schematically represented as follows:
The scientists firstly studied the glycosylation of antibodies targeting enveloped and non-enveloped viruses. They observed that non-fucosylated antibodies are produced to combat enveloped viruses only (as is the case with SARS-CoV-2) but are never produced against non-enveloped viruses. They then analyzed this antibody response in the case of vaccination. They noted that non-fucosylated antibodies are produced after vaccination with an attenuated whole virus, whereas this is not the case with a subunit vaccine (against hepatitis B, for example). Finally, these researchers analyzed the antibody response in the case of infection by SARS-CoV-2. It appears that there is a non-fucosylated antibody response in severe cases of COVID-19, but none in moderate cases.
The production of non-fucosylated antibodies triggers a significant inflammatory response in the respiratory passages, which may be responsible for distress in severe cases of COVID-19. This discovery may be useful in the development of drugs against COVID-19. In serotherapies, for example, the serums must be enriched with fucosylated antibodies to avoid the disease flaring up.