Some Human Anti-Glycan Antibodies Lack the Ability to Activate the Complement System

• Published in: Antibodies (Basel) 2024-12, Vol.13 (4), p.105
• Main Authors: Shilova, Nadezhda, Nokel, Alexey, Lipatnikov, Alexander, Khasbiullina, Nailya, Knirel, Yuri, Baidakova, Ludmila, Tuzikov, Alexander, Khaidukov, Sergei, Obukhova, Polina, Henry, Stephen, Shoibonov, Batozhab, Salimov, Emin, Rieben, Robert, Bovin, Nicolai
• Format: Article
• Language: English
• Subjects: ABO system; anti-glycan antibodies; Antibodies; Antigens; Arrays; B cells; Bacteria; Biological membranes; Biological products; Blood & organ donations; Blood groups; Complement; Complement component C3; Complement system; Deposition; E coli; Erythrocytes; Escherichia coli; Ethylenediaminetetraacetic acid; Glycan; Glycopeptides; Human performance; Immunoglobulin G; Immunoglobulin M; Immunoglobulins; kodecytes; Lectins; Microbial polysaccharides; O-antigens; Polysaccharides; printed glycan array; Saccharides; Solid phases; Target detection
• ISSN: 2073-4468; 2073-4468
• DOI: 10.3390/antib13040105

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. It was found that about 30% of anti-glycan antibodies in human serum detected by the PGA did not activate the complement. They were mostly IgGs and directed to bacterial -antigens; no apparent common structural motif within their target polysaccharides was found. Antibodies to blood group systems ABO and Forssman, xeno-antigens, a number of polysaccharides from various strains of , and , as well as small fragments of bacterial polysaccharides were recognized by complement-activating antibodies as expected. A complement-activating antibody was affinity-isolated on glycan-Sepharose from human serum, and, in the presence of the complement, it lysed red blood cells coated with the same glycan (kodecytes, where glycans expressed on biological membranes), while an isolated complement non-activating antibody did not, which confirms the validity of the solid-phase PGA results. Thus, ~30% of human anti-glycan antibodies lack the ability to activate the complement system. The function of the widely represented immunoglobulins that do not cause C3 deposition remains unclear.