P Blood Group System

P Blood System

• ISBT symbols are P1PK (003), P & PX2 [GLOB] (028), and LKE [GLOB Collection] (209).
• The P1Pk gene is at chromosome 22, and the P gene is at chromosome 3
• The P1PK gene encodes A4GALT (4-Alpha-Galactosyltransferase).
• The GLOBOSIDE gene encodes B3GALNT1 (3-Beta-N-acetylgalactosaminyltransferase).
• P1, Pk, and P antigens exist
• Pk is the precursor of the big "P" antigen
• The identifiable antibodies are Anti-P1, Anti-PP1Pk, and Anti-P.
• Separation into 3 BGS is because the antigen formation of the 3 BGS are slightly different.
• The founding substance is Lactosylceramide (Gb2) or Ceramidedihexose
• P1PK gene = A4GALT; GLOBOSIDE gene = B3GALNT1

Antigens

• These are found in blood cells, plasma, and other tissues, but not in secretions.
• These are glycosphingolipids
• The precursor chain for P1 is a Type 2 chain, found in RBCs.
• P1, Pk, and P can be found in RBCs, lymphocytes, and WBCs.
• The Big P antigen is found in platelets, epithelial cells, and fibroblasts.
• A4GALT forms P1 and Pk antigens from Lactosylceramide (Gb2).
• B3GALNT1 forms P and PX2 antigens from Globotriosylceramide (Gb3).
• A4GALT further modifies the "P" antigen into the NOR antigen.

Development

• A4GALT (From P1PK Gene) acts on Lactosylceramide to form Pk antigen, the precursor of "P" antigen.
• B3GALNT1 (From GLOBOSIDE Gene) then converts Pk antigen to "P" antigen.
• The globoside related antigens are P and PX2
• A4GALT enzyme further modifies the "P" antigen into the NOR antigen.
• The precursor of P1 is type 2 paragloboside, which then gets acted upon by A4GALT
• B3GALNT1 converts Type 2 paragloboside into PX2 antigen.

Phenotypes & Antibodies

• Consists of P1 and P antigens; Reacts to Anti-P1 and Anti-P reagents in the lab
• Consists of only Pantigens; reacts to urgnts
• No presence of P, P1 or Pk antigens; Reacts to Anti-P1, Anti-P and Anti-Pk
• Like A2 subgroups P2 can produce Anti-P1 because they don't have P1 antigens
• There is a high prevalence of the P1 phenotype (75% of adults.)
• Anti-PP1Pk (Originally called Anti-Tja) has cytotoxic effects on tumors

Characteristics of P1 Antigen

• Expressed poorly at birth
• Strength of the antigen decreases upon storage
• Found in plasma and hydatid cyst fluid (caused by Echinococcus granulosus).
• Hydatid cyst fluid can cause anaphylaxis due to its immunogenic contents.
• May take up to 7 years before expression

Characteristics of Anti-P1 Antibody

• Naturally occurring IgM, rarely IgG
• Not clinically significant
• Can occasionally cause HTR but not HDN
• Counteracted by hydatid cyst fluid to improve detection of clinically important antibodies

Anti-P Autoantibody & Alloantibody

• Autoanti-P is found in Paroxysmal Cold Hemoglobinuria (PCH), targets self antigens
  • In cold temperatures, IgG attaches complement - causes lysis of RBCs.
  • The complement fixation activates in warmer temperatures to cause hemolysis
  • It is detected via Donath-Landsteiner Test
• Alloantibody is a naturally occurring antibody similar to Anti-PP1Pk

Antigens & Diseases

• P1 antigen is a receptor for Streptococcus suis and Pseudomonas aeruginosa
• Pk antigen is an E. coli receptor (HUS), and Shiga toxins (Shigella dysentery)
• P antigen is a Human Parvovirus B19 receptor

Ii Blood System

• ISBT Symbol & Number consists of I-(027) for I gene, and i-(207) for i gene
• I gene is found at Chromosome 6
• Unknown for i production
• Gene product is I gene = IGnT (N-acetyl-glucosaminyltransferase)
• Antigens: I and i
• Enhanced by Ficin and Papain, resistant to DTT and Glycine-acid EDTA
• Reacts best with anti-P1, anti-PP1Pk, and anti-P

History and Characteristics for AB

• The antibodies formed against this BGS reacted to most of the blood specimens that they tested but some did not react
• The antigens that are not reactive to the antibody they termed it as small "i"
• I and i antigens are NOT antithetical
• Formed on the precursor A, B and H chains of RBC
• Formed from type 2 chains in RBCs
• The location of antigens are on other cells and secretions
• Adult form is I, and is branched
• Newborns and cord cells have i, and it is linear
• Small "i" is converted to the Big “I” with age

Reactivity & Antibodies

• On Cord cells, reactivity is high due to the small "i"
• Small "i" cannot be converted to Big"I" on Adult
• Benign autoanti-I is clinically insignificant.
• Pathologic autoanti-I is produced due to M. pneumoniae
• Disease is "Walking Pneumoniae"
• Causes Cold Agglutinin Disease (CAD)

Other AB Characteristics

• Alloanti-i is present w/adult cells
• IgM/IgG
• Rare, associates with infectious mononucleosis

Disease Association - I

• Higher incidence in cold agglutinin disease (CAD)
• Can be secondary to an M. pneumoniae infection
• Can occur due to cataracts (Asians)

U Antigen

• U antigens stand for Universal antigens, that means they are generally inherited
• Found with the inheritance of S and s
• About 85% of S-s- individuals are U-negative (RARE)
• Located on Glycophorin A

MNSsU Blood System

• MNS-002 is its ISBT Symbol & Number.
• They have GYPA and GYPB gene products; Glycophorin A and Glycophorin B
• They are located on Chromosome 4
• The main antigens in this system include M, N, S, s, and U.
• Fully developed with RBCs from birth, but not in secretions
• These antigens are antithetical; differing in amino acid composition in same structure

MNSsU - Easy Degradation

• Located far on Glycophorin A for easy degradation
• Located deep on Glycophorin B

Phenotypes & Antibodies

• There can be NO expression of the MNSs antigens
• Includes U- phenotype, En(a-) phenotype, and Mk phenotype

Common Phenotypes

• U is a high-incidence antigen
• U gene is related to S and s
• Can only have anti-U cells found in less than 1% of Black populations

Antibodies

• Anti-M is usually naturally occurring
  • Does not bind complement
• Anti-S and anti-s are clinically significant
  • Their IgG can bind to complements
• Anti-U will react with S+ or s+ red cells
  • A rare U negative - reacts with <1% of black population

Blood & Enzymes

• A-M and anti-N demonstrate dosage
• Will not react to pre-treated enzyme red cells
• Enzyme pre-treatment is necessary and highlights those significant ABs, that are commonly missed
• Contact rare donor registry because there is higher rates of spontaneous abortions
• MNSsU is destroyed by enzymes, but is useful in clinical detection.
• This makes testing an important part of antibody screening, blood grouping procedures and identifying the antigens