The FORS awakens: review of a blood group system reborn

The presence of the FORS1 antigen on red blood cells was discovered relatively recently, and in 2012, the International Society of Blood Transfusion (ISBT) acknowledged FORS as blood group system number 031. This rare antigen is carried by a glycosphingolipid and formed by elongation of the P antigen. Most people have naturally occurring anti-FORS1 in their plasma. The clinical significance of these antibodies is unknown in the transfusion setting, but they can hemolyze FORS1+ erythrocytes in the presence of complement in vitro. First believed to be part of the ABO system, it was later shown that the gene encoding the glycosyltransferase giving rise to FORS1 expression is GBGT1. This gene had previously been deemed nonfunctional in humans, but a mutation, so far only detected in FORS1+ individuals, restores the enzymatic activity. Tissue distribution of the antigen in FORS1+ individuals has not been studied in detail, although the gene is expressed in several cell types. The antigen itself is known to be a receptor for various pathogens and toxins and has been detected in different forms of cancer, but the implications thereof are not fully understood.