This review summarises present knowledge of the chemistry, immunology, genetics and clinical significance of antibodies in the Lewis and secretor histo- blood group systems. Although red cell serology has laid the foundations for these systems, more recent advances have been made by studying Lewis and related glycoconjugates with monoclonal antibodies, determining structures by mass spectrometry and NMR spectroscopy, identifying enzymes and their specificities, and identifying the genes by molecular biology. The expression of Lewis system antigens is dependent on Lewis and secretor loci. Fucosyltrans- ferases coded by genes at these loci compete and interact with each other and with other transferases to determine an individual’s Lewis and secretor phenotype. Exocrine epithelial cells, mostly of endodermal origin, synthesise the Lewis antigens which, as plasma glycolipids, are secondarily acquired by cells of the peripheral circulation. Phenotyping red cells is often regarded as a simple way of determining the Lewis and sometimes the secretor status of an individual; however, the red cell phenotype is influenced by many factors and may not necessarily reflect someone’s Lewis and secretor genotypes. Two main red cell Lewis groups are usually found, Lewis negative and Lewis positive. In Lewis-negative individuals, the secretor genotype does not affect the Lewis phenotype, but in Lewis-positive individuals, the non-secretor genotype generates the Le(a+b-) phenotype, the secretor genotype causes the Le(a-b+ ) phenotype, and the partial secretor genotype gives rise to the Le(a+b+) phenotype.

Key Points• A new histo-blood group system was discovered, based on the identification of Forssman glycolipid antigen on human red blood cells.• A newly described polymorphism in the GBGT1 gene activates the encoded enzyme to synthesize Forssman antigen. IntroductionCarbohydrate histo-blood group antigens, first recognized on red blood cells (RBCs) in 1900, 1 have been suggested to be part of our innate immune response. 2 Major carbohydrate histo-blood groups in man include the ABO, P1PK, H, Lewis, I, and GLOB systems in which glycoproteins and glycolipids carry immunodominant terminal sugars, 3 defining polymorphic antigens. Other mammals also express carbohydrate histo-blood groups, such as ABO, 4 fucoseless B antigen (Galili), 5 and Forssman (Fs) 6,7 but their expression on RBCs varies among species. Although the biologic function of polymorphic carbohydrates on RBCs is unresolved, these antigens can be used as receptors by pathogens [8][9][10][11] and their expression in tissues and bodily secretions are thus believed to reflect microbial selection. 8 In response to blood-group-mimicking glycans on bacterial surfaces, naturally occurring antibodies with the capacity to neutralize various microorganisms are formed. However, these antibodies also constitute substantial transfusion and transplantation barriers. 3,12 In 1987, 3 families with a supposed ABO subgroup named A pae were reported. 13 Although Helix pomatia lectin reacted strongly and polyclonal anti-A weakly with RBCs from some family members, monoclonal (MAb) anti-A reagents were later shown to be nonreactive, thus presenting an apparent paradox. The biochemical and genetic background of this enigmatic phenotype has remained unknown, as has its biologic consequences. We hypothesized that an explanation may be found by studying the glycolipids of this phenotype. 14 Here we report the identification of Fs glycolipids, normally found only on RBCs of selected nonprimate mammals, are strongly expressed on human A pae RBCs. In nonprimates, Fs antigen is synthesized by Fs synthase (globoside 3-␣-N-acetyl-D-galactosaminyltransferase, EC2.4.1.88), 7 an enzyme homologous to the ABO transferase. We also reveal a genetic polymorphism in the human Fs gene (GBGT1) that alters the enzymatically inactive human protein 15 Methods SamplesFive and 3 RBC units were collected from each of 2 unrelated A pae individuals (A pae #1 and A pae #2, respectively) from 2 of the originally reported families. 13 GlycolipidsGlycolipid preparation. Lysed blood units were thawed and total neutral glycolipids with Ͻ 20 sugar residues were isolated (see supplemental Methods, where control glycolipid preparations are also described; available on the Blood Web site; see the Supplemental Materials link at the top of the online article).Open-column chromatography. Total glycolipids (ϳ 110 mg) from each of A pae #1 and #2 were fractionated by silica chromatography column (5g silica/100 mg lipid; Silica 60, Merck) in a system of chloroform (C) methanol (M) solvent mixes (supplemental Metho...

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Polynesians and Finns have two different molecular alterations in their Jk alleles, both of which can now be determined by polymerase chain reaction.

This review summarises present knowledge of the chemistry, immunology, genetics and clinical significance of antibodies in the Lewis and secretor histo-blood group systems. Although red cell serology has laid the foundations for these systems, more recent advances have been made by studying Lewis and related glycoconjugates with monoclonal antibodies, determining structures by mass spectrometry and NMR spectroscopy, identifying enzymes and their specificities, and identifying the genes by molecular biology. The expression of Lewis system antigens is dependent on Lewis and secretor loci. Fucosyltransferases coded by genes at these loci compete and interact with each other and with other transferases to determine an individual's Lewis and secretor phenotype. Exocrine epithelial cells, mostly of endodermal origin, synthesise the Lewis antigens which, as plasma glycolipids, are secondarily acquired by cells of the peripheral circulation. Phenotyping red cells is often regarded as a simple way of determining the Lewis and sometimes the secretor status of an individual; however, the red cell phenotype is influenced by many factors and may not necessarily reflect someone's Lewis and secretor genotypes. Two main red cell Lewis groups are usually found, Lewis negative and Lewis positive. In Lewis-negative individuals, the secretor genotype does not affect the Lewis phenotype, but in Lewis-positive individuals, the non-secretor genotype generates the Le(a+b-) phenotype, the secretor genotype causes the Le(a-b+) phenotype, and the partial secretor genotype gives rise to the Le(a+b+) phenotype.

RBCs can be created to express normal and novel carbohydrate profiles by inserting synthetic glycolipids into them. Such cells will be useful in creating specialized antigen panels and for quality control purposes.

KODE technology not only enables the creation of artificial transfusion reactions in animal models, but also has the potential to be used clinically in man to determine 24-hour cell survival. The ability to recover the kodecytes for further analysis has valuable research and diagnostic potential.

All ABO MoAbs detect the RBC dominant Type 2 ABO antigens; however, some reagents may show minor reactivity with inappropriate blood group antigens, which needs to be considered when using these reagents in alternative or highly sensitive analytic systems.