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 utilized 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, serological and flowcytometric 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 six other primates, >250 blood donors and Apae family relatives without the Apae phenotype. Transfection experiments and molecular modelling showed that 296Gln reactivates the human Fs synthase. Uropathogenic E.coli containing prsG-adhesin-encoding plasmids agglutinated Apae but not group O cells, suggesting biological implications. Predictive tests for intravascular hemolysis with crossmatch-incompatible sera indicated complement-mediated destruction of Fspositive 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Hematologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Hematology (hsv//eng)

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