Molecular characterization of the human ABO blood group orthologus system in pigs

Nguyen, Dinh-Truong; Choi, Hojun; Jo, Haiin; Kim, J.-H.; Dirisala, Vijaya R.; Lee, K.-T.; Kim, T.-H.; Park, K.-K.; Seo, Kun‐Ho; Park, C.

doi:10.1111/j.1365-2052.2010.02152.x

Cited by 16 publications

(26 citation statements)

References 11 publications

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“…Five and 7 pigs presented the 00 and A0 genotype for the A0 blood group, respectively. No AA genotype was detected, in agreement with results of a previous study (Nguyen et al, 2011). All the pigs were homozygous for the G allele on base pair 307 of the FUT1 gene.…”

Section: Resultssupporting

confidence: 92%

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The A0 blood group genotype modifies the jejunal glycomic binding pattern profile of piglets early associated with a simple or complex microbiota1

Priori

Colombo

Koopmans

et al. 2016

Journal of Animal Science

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The intestinal epithelium glycocalyx sugar motif is an important determinant of the bacterial-host interaction and may be affected in pigs by gut microbiota and by blood group genotype. The aim was to study the effect of intestinal association with different microbiota and A0 blood group genotypes on the expressed glycomic pattern in the small intestine. Twelve caesarean-derived pigs previously associated with a simple association (SA) or complex association (CA) microbiota were selected at 26 to 37 d of age. In each subject, different jejunal loops were perfused for 8 h with enterotoxigenic K88 (ETEC), ETEC fimbriae (F4), (LAM), or a saline control. The piglets were genotyped for A0 blood group and the glycomic profile was evaluated by microscopic screening of lectin binding: peanut agglutinin (PNA), which is galactose specific; agglutinin I (UEA), which is fucose specific; lectin II (MALii), which is sialic acid specific; concavalin A, which is mannose specific; soybean agglutinin (SBA), which is -acetyl-galactosamine specific; and wheat germ agglutinin (WGA), which is -acetyl-glucosamine specific. A0 pigs had fewer UEA-positive cells, MALii-positive cells ( < 0.001), and SBA-positive cells ( < 0.10) than 00 pigs. Simple association pigs had more SBA positive cells ( < 0.01) than CA pigs. Enterotoxigenic K88-perfused intestinal loops had fewer UEA-positive cells ( < 0.01) and WGA positive cells ( < 0.001) cells and more PNA positive cells (only in SA pigs, < 0.01). No effects of introduction of F4 and LAM in the intestinal lumen were observed. The porcine A0 blood group genotype and the luminal presence of ETEC strongly affected the jejunal mucosa glycomic pattern profile whereas an early oral simple or complex microbial association had limited effects. Pig genetic background has relevance on the cross talk between intestinal epithelium glycocalyx sugar motif and ETEC and, ultimately, on the gut microbial colonization in later life.

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Section: Resultssupporting

confidence: 92%

“…The blood of piglets was genotyped for A0 blood groups, following the procedure of Nguyen et al (2011). All the pigs were also tested for the M307 gene polymorphism of fucosyltransferase 1 (FUT1) because it is the first limiting enzyme for the formation of the A blood antigen (Coddens et al, 2007).…”

Section: Methodsmentioning

confidence: 99%

The A0 blood group genotype modifies the jejunal glycomic binding pattern profile of piglets early associated with a simple or complex microbiota1

Priori

Colombo

Koopmans

et al. 2016

Journal of Animal Science

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“…In non-primate animal species unigenic AO polymorphism has been reported of pig, dog, rat, cow, and rabbit43. The molecular mechanism of the porcine AO polymorphism was previously elucidated4445. A major portion of the structural gene, including the entire coding sequence in the last coding exon, was found missing in O alleles from various pig strains.…”

Section: Resultsmentioning

confidence: 99%

An integrative evolution theory of histo-blood group ABO and related genes

Yamamoto

Cid

Yamamoto

et al. 2014

Sci Rep

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The ABO system is one of the most important blood group systems in transfusion/transplantation medicine. However, the evolutionary significance of the ABO gene and its polymorphism remained unknown. We took an integrative approach to gain insights into the significance of the evolutionary process of ABO genes, including those related not only phylogenetically but also functionally. We experimentally created a code table correlating amino acid sequence motifs of the ABO gene-encoded glycosyltransferases with GalNAc (A)/galactose (B) specificity, and assigned A/B specificity to individual ABO genes from various species thus going beyond the simple sequence comparison. Together with genome information and phylogenetic analyses, this assignment revealed early appearance of A and B gene sequences in evolution and potentially non-allelic presence of both gene sequences in some animal species. We argue: Evolution may have suppressed the establishment of two independent, functional A and B genes in most vertebrates and promoted A/B conversion through amino acid substitutions and/or recombination; A/B allelism should have existed in common ancestors of primates; and bacterial ABO genes evolved through horizontal and vertical gene transmission into 2 separate groups encoding glycosyltransferases with distinct sugar specificities.T he human histo-blood group ABO system is crucial in safe blood transfusion and cell/tissue/organ transplantation 1,2 . This system consists in A and B oligosaccharide antigens expressed on red blood cells (RBCs) as glycoproteins and glycolipids and antibodies against those antigens in serum. A and B antigens are also expressed by epithelial and endothelial cells, and in secretor type individuals they are also expressed on mucins secreted by exocrine glands. The immuno-dominant structures of A and B antigens are GalNAca1-.3(Fuca1-.2)Gal-and Gala1-.3(Fuca1-.2)Gal-, respectively. A and B alleles of the ABO genetic locus encode A and B transferases, which respectively transfer an N-acetyl-D-galactosamine (GalNAc) or a D-galactose (Gal) to H substances with an a1,3-glycosidic linkage. H substances with the Fuca1-.2Gal-structure are synthesized by fucosylation catalyzed by a1,2-fucosyltransferases (a1,2-FTs) encoded by FUT1/FUT2/SEC1 genes. FUT1-encoded a1,2-FTs and FUT2/SEC1-encoded a1,2-FTs exhibit distinct acceptor substrate specificity, and are differentially expressed amongst tissues. In humans SEC1 is a pseudogene and FUT2 gene presents frequent null alleles so that about 20% of individuals are incapable of expressing either H, A, or B antigens in secretions (nonsecretor type). In the absence of a1,2-FTs no H antigens are produced. Therefore, A/B transferases function only when at least one active a1,2-FT is simultaneously present.In 1990 we correlated the nucleotide sequences of A, B, and O allelic cDNAs and the expression of A and B antigens, and elucidated the molecular genetic basis of human histo-blood group ABO system 3,4 . Four amino acid substitutions (Arg176Gly, Gly235Ser, Leu266Met, an...

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“…The currently identified immunogenic EC carbohydrate antigens include Gal, glycans modified with N‐glycolylneuraminic acid (Neu5Gc), and a carbohydrate antigen (SDa) produced by the porcine β1,4 N‐acetylgalactosaminyltransferase‐2 (B4GALNT2). The human blood group A antigen is also potentially immunogenic; however, high rates of A‐type blood group polymorphism in the pig permit exclusion of this antigen by selective breeding . Collectively, antibody reactivity to the 3 major xenogeneic glycans, Gal, Neu5Gc‐modified glycans, and SDa, accounts for the majority of preformed human anti‐pig antibody reactivity …”

Section: Introductionmentioning

confidence: 99%

“…The human blood group A antigen is also potentially immunogenic 14 ; however, high rates of A-type blood group polymorphism in the pig permit exclusion of this antigen by selective breeding. 15,16 Collectively, antibody reactivity to the 3 major xenogeneic glycans, Gal, Neu5Gc-modified glycans, and SDa, accounts for the majority of preformed human anti-pig antibody reactivity. 17,18 Humans, but not NHPs, make an array of antibodies to Neu5Gc-modified glycans.…”

Section: Introductionmentioning

confidence: 99%

B4GALNT2 and xenotransplantation: A newly appreciated xenogeneic antigen

Byrne

Ahmad-Villiers

et al. 2018

Xenotransplantation

101

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Analysis of non-Gal antibody induced after pig-to-baboon cardiac xenotransplantation identified the glycan produced by porcine beta-1,4-N-acetyl-galactosaminyltransferase 2 (B4GALNT2) as an immunogenic xenotransplantation antigen. The porcine B4GALNT2 enzyme is homologous to the human enzyme, which synthesizes the human SDa blood group antigen. Most humans produce low levels of anti-SDa IgM which polyagglutinates red blood cells from rare individuals with high levels of SDa expression. The SDa glycan is also present on GM2 gangliosides. Clinical GM2 vaccination studies for melanoma patients suggest that a human antibody response to SDa can be induced. Expression of porcine B4GALNT2 in human HEK293 cells results in increased binding of anti-SDa antibody, and increased binding of Dolichos biflorus agglutinin (DBA) a lectin commonly used to detect SDa. In pigs, B4GALNT2 is expressed by vascular endothelial cells and endothelial cells from a wide variety of pig backgrounds stain with DBA suggesting that porcine vascular expression of B4GALNT2 is not polymorphic. Mutations in B4GALNT2 have been engineered in mice and pigs. In both species, the B4GALNT2-KO animals are apparently normal and no longer show evidence of SDa antigen expression. Pig tissues with a mutation in B4GALNT2, added to a background of alpha-1,3-galactosyltransferase deficient (GGTA1-KO) and cytidine monophosphate-N-acetylneuraminic acid hydroxylase deficient (CMAH-KO), show reduced antibody binding, confirming the presence of B4GALNT2 dependent antibodies in both humans and nonhuman primates. Preclinical xenotransplantation using B4GALNT2 deficient donors has recently been reported. Elimination of this source of immunogenic pig antigen should minimize acute injury by preformed anti-pig antibody and eliminate an induced clinical immune response to this newly appreciated xenotransplantation antigen.

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Molecular characterization of the human ABO blood group orthologus system in pigs

Cited by 16 publications

References 11 publications

The A0 blood group genotype modifies the jejunal glycomic binding pattern profile of piglets early associated with a simple or complex microbiota1

The A0 blood group genotype modifies the jejunal glycomic binding pattern profile of piglets early associated with a simple or complex microbiota1

An integrative evolution theory of histo-blood group ABO and related genes

B4GALNT2 and xenotransplantation: A newly appreciated xenogeneic antigen

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