The P1PK blood group system: revisited and resolved

Abstract

This update on the P1PK blood group system (Hellberg Å, Westman JS, Thuresson B, Olsson ML. P1PK: the blood group system that changed its name and expanded. Immunohematology 2013;29:25–33) provides recent findings concerning the P1PK blood group system that have both challenged and confirmed old theories. The glycosphingolipids can no longer be considered the sole carriers of the antigens in this system because the P1 antigen has been detected on human red blood cell glycoproteins. New indications suggest that P1Pk synthase activity truly depends on the DXD motif, and the genetic background and molecular mechanism behind the common P1 and P2 phenotypes were found to depend on transcriptional regulation. Transcription factors bind the P1 allele selectively to a motif around rs5751348 in a regulatory region of A4GALT, which enhances transcription of the gene. Nonetheless, unexplained differences in antigen expression between individuals remain.

ABO blood group antigens and differential glycan expression: Perspective on the evolution of common human enzyme deficiencies

“…The P1PK blood group system includes P1, P k , and NOR antigens ( ISBT, 2021 ). The P1P k synthase enzyme (α(1,4)-galactosyltransferase) is encoded by the A4GALT gene and acts on paragloboside to synthesize P1 antigen and on lactosylceramide to synthesize P k antigen ( Cohn et al., 2020 ; Hellberg et al., 2013b ; Stenfelt et al., 2020 ). The P k antigens are found where P antigens are located, whereas P1 antigens are mostly found on RBCs ( Cohn et al., 2020 ).…”

“…These two phenotypes occur because of an SNP in a transcription factor binding motif (rs5751348) in intron 1 of the A4GALT gene ( Cohn et al., 2020 ; Hellberg et al., 2013b ; Stenfelt et al., 2020 ; Thuresson et al., 2011 ). These mutations can impact the binding of EGR1, RUNX1, and, perhaps, KLF1 transcription factors ( Stenfelt et al., 2020 ). Consequently, decreased expression of the P1P k synthase results in reduced amounts of the P k antigen, and no P1 antigen is synthesized.…”

“…Anti-P1 is usually a naturally occurring, room temperature reactive IgM antibody that does not usually cause HTRs or HDFN ( Cohn et al., 2020 ; Reid and Olsson, 2012 ; Stenfelt et al., 2020 ). Titers of anti-P1 are increased in individuals with fascioliasis, hydatid cyst disease (caused by Echinococcus tapeworms), and in those working closely with birds.…”

“…Anti-PX2 antibodies may be a mixture of IgG and IgM, but little else is known. Anti-PP1P k antibodies are naturally occurring anti-P, anti-P1, and anti-P k antibodies ( Cohn et al., 2020 ; Reid and Olsson, 2012 ; Stenfelt et al., 2020 ). Anti-PP1P k antibodies can cause HTRs and HDFN.…”

“…Less than 0.1% of individuals are deficient in B3GALNT1 or A4GALT. The NOR antigen is created by a variant form of A4GALT found in less than 0.1% of individuals ( Cohn et al., 2020 ; Stenfelt et al., 2020 ).…”