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Forssman expression on human erythrocytes: biochemical and genetic evidence of a new histo-blood group system

Svensson, Lola ; Hult, Annika LU ; Stamps, Robert ; Angstrom, Jonas ; Teneberg, Susann ; Storry, Jill LU ; Jorgensen, Rene ; Rydberg, Lennart ; Henry, Stephen M. and Olsson, Martin L LU (2013) In Blood 121(8). p.1459-1468
Abstract
In analogy with histo-blood group A antigen, Forssman (Fs) antigen terminates with alpha 3-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... (More)
In analogy with histo-blood group A antigen, Forssman (Fs) antigen terminates with alpha 3-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. (Blood. 2013;121(8):1459-1468) (Less)
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publishing date
type
Contribution to journal
publication status
published
subject
in
Blood
volume
121
issue
8
pages
1459 - 1468
publisher
American Society of Hematology
external identifiers
  • wos:000321750000032
  • scopus:84874402159
  • pmid:23255552
ISSN
1528-0020
DOI
10.1182/blood-2012-10-455055
language
English
LU publication?
yes
id
f7cdbd90-4338-41df-9a26-30da9b78fe0a (old id 3979324)
date added to LUP
2016-04-01 10:27:33
date last changed
2020-10-07 01:38:24
@article{f7cdbd90-4338-41df-9a26-30da9b78fe0a,
  abstract     = {In analogy with histo-blood group A antigen, Forssman (Fs) antigen terminates with alpha 3-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. (Blood. 2013;121(8):1459-1468)},
  author       = {Svensson, Lola and Hult, Annika and Stamps, Robert and Angstrom, Jonas and Teneberg, Susann and Storry, Jill and Jorgensen, Rene and Rydberg, Lennart and Henry, Stephen M. and Olsson, Martin L},
  issn         = {1528-0020},
  language     = {eng},
  number       = {8},
  pages        = {1459--1468},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {Forssman expression on human erythrocytes: biochemical and genetic evidence of a new histo-blood group system},
  url          = {http://dx.doi.org/10.1182/blood-2012-10-455055},
  doi          = {10.1182/blood-2012-10-455055},
  volume       = {121},
  year         = {2013},
}