Emergence and significance of carbohydrate-specific antibodies

Abstract

Carbohydrate-specific antibodies are widespread among all classes of immunoglobulins. Despite their broad occurrence, little is known about their formation and biological significance. Carbohydrate-specific antibodies are often classified as natural antibodies under the assumption that they arise without prior exposure to exogenous antigens. On the other hand, various carbohydrate-specific antibodies, including antibodies to ABO blood group antigens, emerge after the contact of immune cells with the intestinal microbiota, which expresses a vast diversity of carbohydrate antigens. Here we explore the development of carbohydrate-specific antibodies in humans, addressing the definition of natural antibodies and the production of carbohydrate-specific antibodies upon antigen stimulation. We focus on the significance of the intestinal microbiota in shaping carbohydrate-specific antibodies not just in the gut, but also in the blood circulation. The structural similarity between bacterial carbohydrate antigens and surface glycoconjugates of protists, fungi and animals leads to the production of carbohydrate-specific antibodies protective against a broad range of pathogens. Mimicry between bacterial and human glycoconjugates, however, can also lead to the generation of carbohydrate-specific antibodies that cross-react with human antigens, thereby contributing to the development of autoimmune disorders.

Glycans of SARS-CoV-2 Spike Protein in Virus Infection and Antibody Production

“…Hennet, 2020). Previous studies have demonstrated that autoimmune diseases, like Guillain-Barre syndrome, multiple sclerosis, and inflammatory bowel disease, are caused by carbohydrate-specific antibodies related to bacterial infection or gut microbes (Kappler and Hennet, 2020). A recent SARS-CoV-2 study showed that COVID-19 patients have unusually high IgM and IgG antibodies to self-carbohydrates, including gangliosides, N-linked glycans, LacNAc derivatives, blood group H1, and sialyl Lewis X (Butler and Gildersleeve, 2020), indicating the possibility of autoimmune disorders caused by these antibodies.…”

Acceptive Immunity: The Role of Fucosylated Glycans in Human Host–Microbiome Interactions

“…The subset of B cells absent from the fetal omentum are B2 cells. B2 and B1b cells are the predominant progenitors of immunoglobulin-producing plasma cells [ 218 ]. B1a cells are the main producers of the so-called natural antibodies, which, despite their microbiota-reactive specificity, can arise in the absence of exogenous microbiota and are represented mainly by antibodies of the IgM class, as well as IgA and IgG [ 219 ].…”

“…The function of natural antibodies is not known. By the eighth month of an infant’s life, the appearance of antibodies produced by B2 cells recognizing ABO and α-Gal antigens in addition to natural IgM indicates the maturation of specific antibodies to these antigens [ 218 ].…”

“…Besides intestinal antibodies, serum IgG and IgA targeted to intestinal bacterial glycans that recognize the glycan epitopes of both commensal and pathogenic bacteria have also been found [ 218 ]. Produced mainly by the TD pathway due to inflammation or dysbiosis, serum IgAs against intestinal bacteria trigger a stronger and more specific immune response [ 242 ].…”

Carbohydrates-based diagnosis, prophylaxis and treatment of infectious diseases: Special emphasis on COVID-19

“…The carbohydrates serve as a chief category of viral antigens which are easily identified by the host immune system that stimulates the production of Abs ( Katharina & Thierry, 2020 ). Thus, carbohydrates are called immunogen or antigen because they are able to induce as well to increase the immune response in the host.…”