Some Human Anti-Glycan Antibodies Lack the Ability to Activate the Complement System
Nadezhda Shilova,
Alexey Nokel,
Alexander Lipatnikov,
Nailya Khasbiullina,
Yuri Knirel,
Ludmila Baidakova,
Alexander Tuzikov,
Sergei Khaidukov,
Polina Obukhova,
Stephen Henry,
Batozhab Shoibonov,
Emin Salimov,
Robert Rieben,
Nicolai Bovin
Affiliations
Nadezhda Shilova
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of Science, 117991 Moscow, Russia
Alexey Nokel
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of Science, 117991 Moscow, Russia
Alexander Lipatnikov
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of Science, 117991 Moscow, Russia
Nailya Khasbiullina
National Medical Research Center for Obstetrics, Gynecology and Perinatology of the Ministry of Health of the Russian Federation, 117991 Moscow, Russia
Yuri Knirel
Zelinsky Institute of Organic Chemistry Russian Academy of Science, 119991 Moscow, Russia
Ludmila Baidakova
Branch of the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, 142290 Pushchino, Moscow Region, Russia
Alexander Tuzikov
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of Science, 117991 Moscow, Russia
Sergei Khaidukov
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of Science, 117991 Moscow, Russia
Polina Obukhova
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of Science, 117991 Moscow, Russia
Stephen Henry
School of Engineering, AUT University, Auckland 92006, New Zealand
Batozhab Shoibonov
Federal Research Center for Original and Promising Biomedical and Pharmaceutical Technologies, 125315 Moscow, Russia
Emin Salimov
Clinical Center of Sechenov First Moscow State Medical University of the Ministry of Health Care of the Russian Federation, 119435 Moscow, Russia
Robert Rieben
Department for BioMedical Research, University of Bern, 3008 Bern, Switzerland
Nicolai Bovin
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of Science, 117991 Moscow, Russia
Background. 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. Methods. 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. Results. 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 O-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 S. enterica, E. coli and P. alcalifaciens, 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. Conclusions. 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.
