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
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of Science, 117991 Moscow, Russia.
National Medical Research Center for Obstetrics, Gynecology and Perinatology of the Ministry of Health of the Russian Federation, 117991 Moscow, Russia.
Antibodies (Basel). 2024 Dec 23;13(4):105. 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.
天然存在的针对聚糖的人类抗体能够识别并快速清除传染性细菌、病毒以及异常糖基化的肿瘤恶性细胞，并且它们常常启动涉及补体系统的过程。我们使用包含605种糖配体（寡糖和多糖、糖肽）的印刷聚糖阵列（PGA），来检测哪些聚糖结合抗体能够激活补体系统。利用该PGA，在健康供体（大多被认为是天然的）的血清中确定了IgM和IgG类抗体的特异性，然后，使用相同的阵列，确定哪些类型的结合免疫球蛋白也显示出C3沉积。结果发现，PGA检测到的人血清中约30%的抗聚糖抗体不激活补体。它们大多是IgG，针对细菌抗原；在其靶多糖中未发现明显的共同结构基序。正如预期的那样，补体激活抗体识别ABO血型系统和福斯曼血型系统的抗体、异种抗原、来自各种菌株的多种多糖以及细菌多糖的小片段。一种补体激活抗体从人血清中在聚糖琼脂糖上进行亲和分离，并且在补体存在的情况下，它裂解涂有相同聚糖的红细胞（编码细胞，其中聚糖在生物膜上表达），而分离出的补体非激活抗体则不能，这证实了固相PGA结果的有效性。因此，约30%的人类抗聚糖抗体缺乏激活补体系统的能力。广泛存在的不引起C3沉积的免疫球蛋白的功能仍不清楚。
