Roles of Anti-glycan Antibodies in Human Diseases

Molecules with glycosidic bonds can be generally described as glycans, for example, sugar, including polysaccharides and carbohydrates. Glycans are the main components of the surfaces of erythrocytes, immune cells, microorganisms, etc., which results in the high-level production of anti-glycan antibodies. A large number of anti-glycan antibodies are discovered in human sera as potential biomarkers of cancers.

Anti-glycan Antibodies in Diseases

Anti-glycan antibodies, or known as carbohydrate-binding antibodies, exert critical influence in the diagnosis and prognosis of human diseases. Anti-glycan antibodies can recognize bacterial, fungal, and other microbial carbohydrates and induce immune responses to prevent systemic infections and maintain microbiome homeostasis.

However, such immune responses triggered by anti-glycan antibodies could be both detrimental and beneficial. For instance, endogenous anti-glycan antibodies could cause autoimmune diseases like Guillain-Barre syndrome, while several developed vaccines induce anti-glycan antibodies primarily for a protective mechanism on human health. In addition to be developed as vaccines, certain monoclonal anti-glycan antibodies are developed for diagnostic and therapeutic purposes in diseases.

Anti-Glycan Antibodies in Diagnostics and Prognosis

Similar to other antibodies, the application of natural and prepared anti-glycan antibodies in diagnostics has been widely accepted and acclaimed in laboratory research and clinical trials.

With glycan arrays for systematic screening of the patient blood samples versus those from control groups, researchers have discovered a few anti-glycan antibodies biomarkers that can contribute to the diagnosis and prognosis of multiple sclerosis (MS) and Crohn’s disease (CD) patients. Studies also show that anti-polysaccharide antibodies provide a possible diagnostic value for colorectal cancer, ulcerative colitis, and other gastrointestinal diseases, though further validation of these biomarkers in a large independent cohort is required.

More and more newly investigated anti-glycan antibodies are suggested to be potential biomarkers used for diagnostics and prognosis with higher specificity and sensitivity.

Anti-glycan Antibodies in Therapeutics

Even though the development of anti-glycan antibodies relatively falls behind that of anti-protein antibodies and anti-peptide antibodies, anti-glycan antibodies in therapeutics still exhibit great potential in terms of their specificity and targeting properties to carbohydrates-based antigens.

Anti-glycan antibodies can bind to the surface of cells and certain carbohydrates and stimulate immune responses to attack antigens in the body, which makes them possible therapeutics for immune-related diseases and advances the development of vaccines strategies.

Anti-glycan Antibodies in Vaccines

Anti-glycan antibodies could either be produced through natural processes or induced by a variety of vaccines. Up to now, there are some approved carbohydrate-based vaccines against pneumococcus, Haemophilus influenzae type b, and Neisseria meningitidis.

Researchers recently identified a new type of anti-glycan antibody with a special shape that can specifically bind to a patch of the chain-like sugars on the outer shell of HIV and effectively neutralize the virus. And anti-glycan antibodies are anticipated to be used against SARS-CoV-2 and fungal pathogens in that a lot of pathogens can express surface glycans, including HIV Envelope (Env), the SARS-CoV-2 spike protein, and yeast. Actually, more than 50% of the outer layer of HIV is comprised of glycans, which entices researchers to explore a way of releasing anti-glycan antibodies to break down these sugar structures of HIV, triggering immune B-cell lymphocytes to produce antibodies that could then neutralize HIV.

Summary

The membrane surface of cells with different functions contains various carbohydrates and glycan chains which can be specifically targeted by the anti-glycan antibodies. Therefore, anti-glycan antibodies are expected to play a critical role in human diseases, including working as vehicles or carriers for the targeted drug delivery. In conclusion, further research on anti-glycan antibodies could unlock a new perspective for targeted cancer therapies, as well as for the diagnosis and prognosis of other human diseases.