title: Forssman expression on human erythrocytes: biochemical and genetic evidence of a new histo-blood group system.
abstract: In analogy with histo-blood group A antigen, Forssman (Fs) antigen terminates with α3-N-acetylgalactosamine and can be used by pathogens as a host receptor in many mammals. However, primates including humans lack Fs synthase activity and have naturally occurring Fs antibodies in plasma. We investigated individuals with the enigmatic ABO subgroup A(pae) and found them to be homozygous for common O alleles. Their erythrocytes had no A antigens but instead expressed Fs glycolipids. The unexpected Fs antigen was confirmed in structural, serologic, and flow-cytometric studies. The Fs synthase gene, GBGT1, in A(pae) individuals encoded an arginine to glutamine change at residue 296. Gln296 is present in lower mammals, whereas Arg296 was found in 6 other primates, > 250 blood donors and A(pae) family relatives without the A(pae) phenotype. Transfection experiments and molecular modeling showed that Agr296Gln reactivates the human Fs synthase. Uropathogenic E coli containing prsG-adhesin-encoding plasmids agglutinated A(pae) but not group O cells, suggesting biologic implications. Predictive tests for intravascular hemolysis with crossmatch-incompatible sera indicated complement-mediated destruction of Fs-positive erythrocytes. Taken together, we provide the first conclusive description of Fs expression in normal human hematopoietic tissue and the basis of a new histo-blood group system in man, FORS.
authors.affiliation: Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
authors.forename: Lola
authors.initials: L
authors.lastname: Svensson
authors.forename: Annika K
authors.initials: AK
authors.lastname: Hult
authors.forename: Robert
authors.initials: R
authors.lastname: Stamps
authors.forename: Jonas
authors.initials: J
authors.lastname: Ångström
authors.forename: Susann
authors.initials: S
authors.lastname: Teneberg
authors.forename: Jill R
authors.initials: JR
authors.lastname: Storry
authors.forename: René
authors.initials: R
authors.lastname: Jørgensen
authors.forename: Lennart
authors.initials: L
authors.lastname: Rydberg
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Henry
authors.forename: Martin L
authors.initials: ML
authors.lastname: Olsson
mesh_terms: D000017:ABO Blood-Group System / Q000235:genetics; D001788:Blood Grouping and Crossmatching / Q000379:methods*; D002240:Carbohydrate Sequence; D002855:Chromatography, Thin Layer; D004912:Erythrocytes / Q000502:physiology*; D004926:Escherichia coli / Q000201:enzymology; D005577:Forssman Antigen / Q000235:genetics* / Q000378:metabolism*; D005838:Genotype; D006386:Hemagglutination Tests; D006801:Humans; D008956:Models, Chemical; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D017350:N-Acetylgalactosaminyltransferases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000502:physiology; D017434:Protein Structure, Tertiary
chemical_list: D000017:ABO Blood-Group System; D005577:Forssman Antigen; D017350:N-Acetylgalactosaminyltransferases; C023216:globoside alpha-N-acetylgalactosaminyltransferase