Humans and other animals produce a diverse collection of antibodies, many of which bind to carbohydrate chains, referred to as glycans. These anti-glycan antibodies are a critical part of our immune systems' defenses. Whether induced by vaccination or natural exposure to a pathogen, anti-glycan antibodies can provide protection against infections and cancers. Alternatively, when an immune response goes awry, antibodies that recognize self-glycans can mediate autoimmune diseases. In any case, serum anti-glycan antibodies provide a rich source of information about a patient's overall health, vaccination history, and disease status. Glycan microarrays provide a high-throughput platform to rapidly interrogate serum anti-glycan antibodies and identify new biomarkers for a variety of conditions. In addition, glycan microarrays enable detailed analysis of the immune system's response to vaccines and other treatments. Herein we review applications of glycan microarray technology for serum anti-glycan antibody profiling.
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http://dx.doi.org/10.1039/d3cs00693j | DOI Listing |
Antibodies (Basel)
December 2024
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of Science, 117991 Moscow, Russia.
Naturally occurring human antibodies against glycans recognize and quickly eliminate infectious bacteria, viruses and aberrantly glycosylated neoplastic malignant cells, and they often initiate processes that involve the complement system. Using a printed glycan array (PGA) containing 605 glycoligands (oligo- and polysaccharides, glycopeptides), we examined which of the glycan-binding antibodies are able to activate the complement system. Using this PGA, the specificities of antibodies of the IgM and IgG classes were determined in the blood serum of healthy donors (suggested as mostly natural), and, then, using the same array, it was determined which types of the bound immunoglobulins were also showing C3 deposition.
View Article and Find Full Text PDFCell Chem Biol
December 2024
Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA. Electronic address:
Polysaccharide intercellular adhesin (PIA), an exopolysaccharide composed of poly-N-acetyl glucosamine (PNAG), is an essential component in many pathogenic biofilms. Partial deacetylation of PNAG is required for biofilm formation, but limited structural knowledge hinders therapeutic development. Employing a new monoclonal antibody (TG10) that selectively binds highly deacetylated PNAG and an antibody (F598) in clinical trials that binds highly acetylated PNAG, we demonstrate that PIA within the biofilm contains distinct regions of highly acetylated and deacetylated exopolysaccharide, contrary to the previous model invoking stochastic deacetylation throughout the biofilm.
View Article and Find Full Text PDFbioRxiv
October 2024
Department of Microbiology, University of Alabama at Birmingham Heersink School of Medicine, Birmingham AL 35294, USA.
The human antibody repertoire is broadly reactive with carbohydrate antigens represented in the universe of all living things, including both the host/self- as well as the commensal microflora-derived glycomes. Here we have used BCR receptor cloning and expression together with single-cell transcriptomics to analyze the B cell repertoire to the ubiquitous N-acetyl-D-glucosamine (GlcNAc) epitope in human cohorts and dissect the immune phylogeny of this predominant class of antibodies. We find that circulating anti-GlcNAc B cells exhibiting canonical BMem phenotypes emerge rapidly after birth and couple this observation with evidence for germinal center-dependent affinity maturation of carbohydrate-specific B cell receptors during early childhood.
View Article and Find Full Text PDFTetrahedron
September 2024
Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, USA.
We developed a method for making immune responses to bacterial glycans T cell-dependent, which involves attachment of short, synthetic glycans to a virus-like nanoparticle (VLP). This strategy enhances immune responses to glycans by facilitating cognate T cell help of B cells, leading to antibody class switching and affinity maturation yielding high-affinity, anti-glycan antibodies. This method requires synthesis of bacterial glycans as propargyl glycosides for covalent attachment to VLPs, and the resulting short linker between the VLP and glycan is important for optimal T cell receptor recognition.
View Article and Find Full Text PDFFront Immunol
August 2024
Department of Pathology, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, United States.
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