A study of the formation of ABH antigens

Published: November 27, 2015 Words: 1066

The oligosaccharide responsible for the formation of the A and B antigen can exist in a simple linear fashion or a complex branched fashion. Infants A, B and H antigens contain high amount of linear chained oligosaccharide whereas oligosaccharides present in an adult contain high amount of branched chained oligosaccharides

The A and B antigens were originally detected on erythrocytes by means of isoagglutinins in the serum of persons lacking these determinants. These antigens are synthesized from a common intermediate, H substance, by addition of a single sugar to the noreducing end of H oligosaccharide chains, and the immunologic reactivity of the H antigen is markedly decreased by the additional sugar. There is no O antigen; Group O erythrocytes and the saliva of Group O secretors contain the H antigen, but the designation Group O erythrocytes has been retained for historical reasons. Approximately 75 per cent of white persons secrete glycoproteins containing the same A, B or H antigens present on their erythrocytes.

The Lewis antigens, Lea and Leb, are also found on erythrocytes and glycoproteins. These antigens appear on the same glycoproteins as the ABH determinants, but their synthesis is regulated by the independent gene Le.

ABH substances are secreted by mucous glands in many organs, including the upper respiratory tract, the gastrointestinal tract from the esophagus through the colon and the uterine cervix. The synthesis of blood-group substances in superficial glands of the gastric and small-intestine mucosa is regulated by the secretor gene. Large amounts of ABH material are found all secretors, but abundant Leb substance and no ABH substance is seen in non-secretors. Glands situated more deeply in the mucosa of the pylorus and small intestine (Brunner's glands) produce A and B substances without regard to secretor status. (64,66) These substances are not extracted by fixation of the tissues with alcohol and are probably glycoproteins. The gastric parietal glands also produce A and B substances in both secretors and nonsecretors, but this material is alcohol soluble and is probably glycosphingolipid in nature.(117)

The prostate glands and the lactating mammary glands of secretors also produce ABH substances.(66) The pattern of secretion by the breast is unusual in that abundant H substance is produced by secretors of all ABH phenotypes, but much less A substance, and virtually no B substance, is detectable in the breast or in milk. (69) Synthesis of ABH substances in the exocrine acini of the pancreas and the secre tory cells, of sweat glands is not regulated by the secretor gene. ABH substances are detectable in the plasma of nonsecretors and secretors; the latter tend to have higher titers, but there is considerable overlap between the two groups. (70,71)

Blood-group substances have been detected in the collecting tubules and calyxes of secretors, but it is not clear whether they are synthesized by the kidney or merely excreted.

ABH substances appear in secretions at eight to nine weeks' ovulation age in the salivary glands and stomach, and then appear throughout the gastrointestinal tract and other characteristic locations.

The former found no correlation between alkaline phosphatase levels and ABO groups or secretor type, but the latter observed that Group O and B secretors had the highest mean concentration of alkaline phosphatase, Group A secretors had the next highest concentration, and nonsecretors had the lowest amount. The ABO and secretor genes influence the rate at which the intestinal phosphatase enters the blood, or its catabolism, rather than its synthesis in the intestine.(103)

The association of ABO and secretor types with this serum enzyme polymorphism is of particular interest because of the association of the same traits with certain diseases of the gastrointestinal tract

The ABH antigens are not primary gene products but instead they are the enzymatic reaction products of enzymes called glycosyltransferases. The ABO system occurs as a result of polymorphism of complex carbohydrate structrures of glycoproteins and glycolipids expressed at the surface of erythocytes or other cells, or present in secretions, as glycan units of mucinglycoproteins. Immuno-dominant structures of A and B antigens, GalNAc alpha1->3 (Fuc alpha1->2) Gal- and Gal alpha1->3 (Fuc alpha1->2) Gal-, respectively, are synthesized by a series of reactions; the A and B transferases encoded by the functional alleles (A and B alleles) of a single gene at the ABO locus, catalyze the last step of the synthesis, while the transferase coded by the O allele is non-functional; therefore, the acceptor substrate, (H antigen: Fuc alpha1->2 Gal-) remains without a further modification and the A and B determinants are absent.

Structures of the non-reducing end of the ABH and Lewis blood group antigen determinants.

The ABH and Lewis glycoproteins possess a common basic structure, and their blood-group specificity is determined by the sequence and linkage of sugars at the terminal nonreducing end of the carbohydrate chains. The number of chains bearing antigenic determinants has been estimated at 40 to 100 per 300,000 molecular weight.

It was known early in the century that ABH substances occur in human tissues and secretions in two forms, water-soluble and alcohol-soluble, and that persons with these substances in saliva (secretors) have more water-soluble substances in their tissues than those lacking the substance in their saliva (nonsecretors).

ABH substances are secreted by mucous glands in many organs, including the upper respiratory tract, the gastrointestinal tract from the esophagus through the colon and the uterine cervix. (1) The synthesis of blood-group substances in superficial glands of the gastric and small-intestine mucosa is regulated by the [19q13.3 secretor gene]?. Large amounts of ABH material are found all secretors, but abundant Leb substance and no ABH substance is seen in non-secretors. Glands situated more deeply in the mucosa of the pylorus and small intestine (Brunner's glands) produce A and B substances without regard to secretor status. These substances are not extracted by fixation of the tissues with alcohol and are probably glycoproteins. The gastric parietal glands also produce A and B substances in both secretors and nonsecretors, but this material is alcohol soluble and is probably glycosphingolipid in nature.(2,3,4,5,6,7)

The prostate glands and the lactating mammary glands of secretors also produce ABH substances. (10) Synthesis of ABH substances in the exocrine acini of the pancreas and the secre tory cells, of sweat glands is not regulated by the secretor gene.

Blood-group substances have been detected in the collecting tubules and calyxes of secretors, but it is not clear whether they are synthesized by the kidney or merely excreted.