Harpers

618 / CHAPTER 52antibodies. For purposes of blood transfusion, it is particularlyimportant to know the basics of the ABO andRh systems. However, knowledge of blood group systemsis also of biochemical, genetic, immunologic, anthropologic,obstetric, pathologic, and forensic interest.Here, we shall discuss only some key features of theABO system. From a biochemical viewpoint, the majorinterests in the ABO substances have been in isolatingand determining their structures, elucidating theirpathways of biosynthesis, and determining the naturesof the products of the A, B, and O genes.The ABO System Is of Crucial Importancein Blood TransfusionThis system was first discovered by Landsteiner in 1900when investigating the basis of compatible and incompatibletransfusions in humans. The membranes of thered blood cells of most individuals contain one bloodgroup substance of type A, type B, type AB, or type O.Individuals of type A have anti-B antibodies in theirplasma and will thus agglutinate type B or type ABblood. Individuals of type B have anti-A antibodies andwill agglutinate type A or type AB blood. Type ABblood has neither anti-A nor anti-B antibodies and hasbeen designated the universal recipient. Type O bloodhas neither A nor B substances and has been designatedthe universal donor. The explanation of these findingsis related to the fact that the body does not usually produceantibodies to its own constituents. Thus, individualsof type A do not produce antibodies to their ownblood group substance, A, but do possess antibodies tothe foreign blood group substance, B, possibly becausesimilar structures are present in microorganisms towhich the body is exposed early in life. Since individualsof type O have neither A nor B substances, they possessantibodies to both these foreign substances. Theabove description has been simplified considerably; eg,there are two subgroups of type A: A 1 and A 2 .The genes responsible for production of the ABOsubstances are present on the long arm of chromosome9. There are three alleles, two of which arecodominant (A and B) and the third (O) recessive;these ultimately determine the four phenotypic products:the A, B, AB, and O substances.The ABO Substances AreGlycosphingolipids & GlycoproteinsSharing Common Oligosaccharide ChainsThe ABO substances are complex oligosaccharides presentin most cells of the body and in certain secretions.On membranes of red blood cells, the oligosaccharidesthat determine the specific natures of the ABO substancesappear to be mostly present in glycosphingolipids,whereas in secretions the same oligosaccharidesare present in glycoproteins. Their presence in secretionsis determined by a gene designated Se (for secretor),which codes for a specific fucosyl (Fuc)transferase in secretory organs, such as the exocrineglands, but which is not active in red blood cells. Individualsof SeSe or Sese genotypes secrete A or B antigens(or both), whereas individuals of the sese genotype donot secrete A or B substances, but their red blood cellscan express the A and B antigens.H Substance Is the Biosynthetic Precursorof Both the A & B SubstancesThe ABO substances have been isolated and their structuresdetermined; simplified versions, showing onlytheir nonreducing ends, are presented in Figure 52–6.It is important to first appreciate the structure of the Hsubstance, since it is the precursor of both the A and Bsubstances and is the blood group substance found inpersons of type O. H substance itself is formed by theaction of a fucosyltransferase, which catalyzes the additionof the terminal fucose in α1 → 2 linkage ontothe terminal Gal residue of its precursor:GDP -Fuc + Gal-β-R → Fuc-α12, -Gal-β-R + GDPPrecursorH substanceThe H locus codes for this fucosyltransferase. The h alleleof the H locus codes for an inactive fucosyltransferase;therefore, individuals of the hh genotype cannotgenerate H substance, the precursor of the A and Bantigens. Thus, individuals of the hh genotype will havered blood cells of type O, even though they may possessthe enzymes necessary to make the A or B substances(see below).The A Gene Encodes a GalNAc Transferase,the B Gene a Gal Transferase, & the O Genean Inactive ProductIn comparison with H substance (Figure 52–6), A substancecontains an additional GalNAc and B substancean additional Gal, linked as indicated. Anti-A antibodiesare directed to the additional GalNAc residue foundin the A substance, and anti-B antibodies are directedtoward the additional Gal residue found in the B substance.Thus, GalNAc is the immunodominant sugar(ie, the one determining the specificity of the antibodyformed) of blood group A substance, whereas Gal is theimmunodominant sugar of the B substance. In view ofthe structural findings, it is not surprising that A substancecan be synthesized in vitro from O substance in areaction catalyzed by a GalNAc transferase, employingUDP-GalNAc as the sugar donor. Similarly, blood