P1PK blood group system

P1PK phenotypes

P1PK phenotypes are defined by reactivity to antibodies to anti-P₁, anti-P, anti-P^k anti-PP₁P^k. and anti-NOR antibodies.

• P₁ Phenotype: anti-P₁ (+), anti-P (+) and anti-PP₁P^k (+) and anti-P^k (-).Found in 95% of Blacks and 80% of Caucasians and 30% in Japanese.
• P₂ Phenotype: anti-P₁ (-), anti-P (+), antiPP₁P^k (+), and anti-P^k (-). Found in 5% of Blacks and 20% of Whites.
• Rare p phenotype (absence of P1PK antigens caused by null mutations in A4GALT): anti-P₁ (-), anti-P (-), anti-PP₁P^k (-), and anti-P^k (-). These individuals have a very strong anti-PP₁P^k which can be associated with delayed hemolytic transfusion reactions and early spontaneous abortions or hemolytic disease of the fetus and newborn (HDFN). Currently, 34 alterations, in 37 alleles, in the A4GALT gene have been found to abolish the enzyme activity, giving rise to the rare p phenotype.
• The rare NOR phenotype is caused by the presence of unique NOR1 and NOR2 glycosphingolipid antigens, terminating with Galα1 → 4GalNAcβ1. Such structure, found only in Rana ridibunda, is a result of mutation in the A4GALT gene, leading to p.Q211E substitution in Gb3/CD77 synthase (rs397514502).

P1PK antibodies

• Anti-P1 antibodies are present in up to two-thirds of P₂ individuals, and are usually clinically insignificant. When performing blood transfusion to an anti-P1 positive patient, only rare hemolytic transfusion reactions have been reported. Anti-P1 titers are often elevated in patients with liver flukes (fascioliasis), hydatid cyst disease and who are frequently exposed to birds (which may have P1-like substances in their excrement).
• Anti-P1P^k is composed of a mixture of anti-GLOB, anti-P1 and antiP^k in the serum of p individuals. Alloanti-GLOB is seen in the sera of P₁^k and P₂^k persons and is naturally occurring and predominantly IgM isotype (but may also be a mixture of IgM and IgG). The antibodies are capable of causing hemolytic transfusion reactions and hemolytic disease of the fetus and newborn (if IgG isotype and therefore capable of crossing the placenta). There is a relationship between anti-PP1P^k and early spontaneous abortion (the placenta is rich in P^k and GLOB antigens which are targeted by IgG isotype antibodies).
• Anti-NOR antibodies occur naturally in most individuals. They react with NOR1 and NOR2 antigens, causing a phenomenon called NOR polyagglutination.

Antibody detection

Anti-P1P^k antibodies are not usually detected with routine laboratory methods. It is possible to detect them using the Donath-Landsteiner test. This test is performed on 2 vials of blood at two different temperatures: 4 °C and 37 °C (body temperature). A test is interpreted as positive only after a patient's red blood cells have been incubated at both temperatures and subsequently hemolyzed.

Clinical diagnostic

Clinical testing in patient care for P1PK antigens follows published minimum quality and operational requirements, similar to red cell genotyping for any of the other recognized blood group systems. Molecular analysis can identify gene variants (alleles) that may affect P1PK antigens expression on the red cell membrane.