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

Lola Svensson, Annika K. Hult, Robert Stamps, Jonas Ångström, Susann Teneberg, Jill R. Storry, René Jørgensen, Lennart Rydberg, Stephen M. Henry, Martin L. Olsson*

*Corresponding author

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review


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 Apae 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 Apae 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 Apae family relatives without the Apae phenotype. Transfection experiments and molecular modeling showed that Agr296Gln reactivates the human Fs synthase. Uropathogenic E colicontaining prsG-adhesin-encoding plasmids agglutinated Apae 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.

Udgave nummer8
Sider (fra-til)1459-1468
Antal sider10
StatusUdgivet - 21 feb. 2013
Udgivet eksterntJa

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