Abstract
Humoral immunity to pathogens and other environmental challenges is paramount to maintain normal health, and individuals lacking or unable to make antibodies are at risk. Recent studies indicate that many human protective antibodies are against carbohydrate antigens; however, little is known about repertoires and individual variation of anti-carbohydrate antibodies in healthy individuals. Here we analyzed anti-carbohydrate antibody repertoires (ACARs) of 105 healthy individual adult donors, aged 20–60+ from different ethnic backgrounds to explore variations in antibodies, as defined by binding to glycan microarrays and by affinity purification. Using microarrays that contained > 1,000 glycans, including antigens from animal cells and microbes, we profiled the IgG and IgM ACARs from all donors. Each donor expressed many ACAs, but had a relatively unique ACAR, which included unanticipated antibodies to carbohydrate antigens not well studied, such as chitin oligosaccharides, Forssman-related antigens, globo-type antigens, and bacterial glycans. We also saw some expected antibodies to ABO(H) blood group and α-Gal-type antigens, although these also varied among individuals. Analysis suggests differences in ACARs are associated with ethnicity and age. Thus, each individual ACAR is relatively unique, suggesting that individualized information could be useful in precision medicine for predicting and monitoring immune health and resistance to disease.
Highlights
Humoral immunity to pathogens and other environmental challenges is paramount to maintain normal health, and individuals lacking or unable to make antibodies are at risk
All samples were screened on the NCFGv1 microarray, a designer array that contains 99 glycans, chosen to represent relatively common determinants, including β- and α-glucans, chitins, lacto and globo sialylated series, gangliosides, Forssman and P antigens, Lewis a/b and x antigen types, α-galactosyl antigens (Galα1-3-R), globo- and isoglobo series, as well as the major blood group antigens ABO(H) (Supplementary Table S2 found in Supplementary Data File, includes common names and glycan structures)
Two other glycan microarrays were used to screen a subset of the healthy individuals; the 610-glycan microarray (v5.1) of the Consortium for Functional Glycomics (CFG), and the 313 glycans on the Microbial Glycan Microarray (MGM) of the CFG
Summary
Humoral immunity to pathogens and other environmental challenges is paramount to maintain normal health, and individuals lacking or unable to make antibodies are at risk. It might be predicted that highly individualistic differences in ACARs occur, since environmental exposures, including microbial exposure, are likely be unique to each individual Such information may lead to novel insights into human health and personalized medicine, and perhaps address concerns over the importance of vaccination. Recent technological developments have employed glycan microarray technology[11, 17, 19, 50,51,52] or other array-type s trategies[53, 54] to investigate unique individual ACARs. A few studies have focused on bacterial polysaccharides and blood group a ntigens[18], and used either pooled sera or total immunoglobulins to assess the ACA diversity[13, 14] on a population level. More information is needed in regard to individual differences in ACARs and their relationship to ethnicity, gender and age, as well as exploring recognition of a wider diversity of glycan antigens
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