Anti-glycan IgM repertoires in newborn human cord blood

Abstract

Natural antibodies are an innate-like subset of serum antibodies involved in host defense, tumor surveillance, homeostasis, and autoimmunity. Defining the natural antibody repertoire is critical for identifying biomarkers, developing vaccines, controlling and preventing autoimmunity, and understanding the development and organization of the immune system. While natural antibodies to protein antigens have been studied in depth, little is known about natural antibodies to carbohydrate antigens. To address this, we profiled IgM from umbilical cord blood and matched maternal sera on a glycan microarray. Since standard methods to detect maternal contamination in cord serum did not have sufficient sensitivity for our study, we developed a highly sensitive microarray-based assay. Using this method, we found that over 50% of the cord samples had unacceptable levels of maternal contamination. For the cord samples with high purity, anti-glycan IgM antibodies were prevalent and recognized a broad range of non-human and human glycans. Using principal component analysis and hierarchical clustering, cord IgM repertoires showed a high degree of similarity with each other but were distinct from maternal IgM repertoires. Our results demonstrate that many anti-glycan antibodies in human serum are natural antibodies and provide new insights into the development of anti-glycan antibody repertoires.

Emergence and significance of carbohydrate-specific antibodies

“…The development of functional IgM and IgG repertoires parallels the first contact with the extrauterine environment [92,93], but take several years until completion of antibody maturation [94,95]. Some carbohydrate-specific IgM have been reported in cord blood [96], although they remain marginal in the first weeks of life [97]. Within the first months of life, infants develop carbohydrate-specific antibodies such as ABO-specific IgM [98] and α-Gal antibodies [29,99].…”

Repertoire of naturally acquired maternal antibodies transferred to infants for protection against shigellosis

“…IgM against environmental and vaccine antigens has been reported in cord blood from infants in LMIC but not in those from industrialized nations. The origin of this IgM is unclear and presumed to reflect environmental factors, such as intrauterine infections that affect placenta integrity (42, 43), and non-specific natural antibodies (42, 44). Maternal SBA and OPKA against both serotypes were strongly associated implying shared antibody contribution to microbial killing.…”

Corpora Amylacea in the Human Brain Exhibit Neoepitopes of a Carbohydrate Nature

“…In addition, natural IgM antibodies have been described to recognize some carbohydrates, such as advanced glycation end products, whose production is increased with aging ( 37 , 44 – 48 ). In fact, many α-glycan antibodies present in human sera belong to the IgM class and are natural antibodies ( 49 ). In any case, IgMs often recognize epitopes that act as markers of own residual structures ( 42 ) and, as mentioned previously, CA contain some of these residual structures.…”