5 Other Major Blood Group Systems

• MNS blood group system is composed of 43 antigens

  • Landsteiner and Levine immunized rabbits with human RBCs
  • Anti-M and Anti-N were reported (1927)
  • M and N-antithetical antigens
  • Wash and Montgomery discovered S antigen
  • In 1951, s antigen was discovered
  • Wiener discovered U antigen
• M and N Antigens (MNS blood group) are found on glycophorin A that is found in the surface of RBC

  • Well developed at birth
  • Easily destroyed by enzymes ficin, papain, bromelin, trypsin and pronase
  • Also destroyed *ZZAP (Dithiothreitol (DTT) + ficin/papain)
  • Not affected by DTT alone
• S and s antigens (MNS blood group) are located on a smaller glycoprotein → Gycophorin B

  • Differentiated by the amino acid 29th position
  • S – methionine
  • s - threonine
  • Well developed at birth
  • Less easily degraded by enzymes
  • Destroyed by ficin, papain, bromelin, pronase and chymotrypsin
• Anti-M (MNS blood group) is a naturally occurring saline agglutinin (can occur without exposure to antigen)

  • Reacts at <37°C
  • 50-80% are IgG
  • Do not bind complement regardless of Ab class
  • Do not react with enzyme-treated cells
  • Reacts better with MM genotypes than with MN genotypes
  • Some reacts best at pH 6.5
  • Some may react only to RBCs exposed to glucose
  • Clinically insignificant as long it does not react at 37°C
  • Rarely causes HTR or HDN
• Anti-N are cold-reactive IgM or IgG saline agglutinin (MNS blood group)

  • Does not bind complement
  • Does not react with enzyme-treated cells because they are easily destroyed by enzymes
  • Demonstrate dosage effect
  • Clinically insignificant unless reactive at 37°C
  • Implicated in rare cases of HDN
  • Also seen in renal patients who are dialyzed on equipment sterilized by formaldehyde
• Dosage effect is the phenomenon wherein your antibodies react stronger in homozygous RBCs than heterozygous blood cells
• Damage of M and N antigen due to exposure to formaldehyde produces the anti-Nf antibodies

  • associated with rejection of chilled transplanted kidneys
• Anti-S and Anti-s (MNS blood group) are clinically significant

  • IgG, reactive at 37°C and AHG phase
  • Demonstrate dosage effect
  • May or may not react with enzyme-treated cells (less destroyed by enzymes)
  • More significant compared to anti M and anti N
  • May bind complement and have been implicated in severe HTR and HDN
• MNS system is found on chromosome 4
• Anti-M lectin:

  • Iberis amara → causes agglutination when mixed with RBC
• Anti-N lectins:

  • Bauhinia variegata
  • Bauhinia purpurea
  • Vicea graminea
• U phenotype is a universal antigen, located on GPB (MNS blood group)

  • High incidence antigen (>90% in population)
• Anti-U (MNS blood group) is produced by individuals who lack GPB and IgG; has been reported to cause HTR and HDN
• GPA may serve as receptor for certain pyelonephrogenic strain of Escherichia coli
• GPA, GPB, GPC may serve as receptors for P. falciparum
• P blood group system is composed of P, P1 , Pk , Luke*

  • It cannot be considered as a single blood group
  • At least 2 biosynthetic pathways and genes located at different loci
  • Phenotypes: P+ and P-
  • Additional phenotypes: P1 k and P2 k
• Landsteiner and Levine injected human RBCs to Rabbits in 1927, and produced the anti-P
• Levine in 1951, described anti-Tja (anti-PP1 Pk), which is produced by P null individuals
• Matson et al in 1959, described pk, which is expressed in all RBCs except in p phenotype
• P1 Antigen (P blood group) is found on fetal RBCs during 12 weeks but weakens with gestational age

  • Poorly expressed at birth and fully expressed at 7 years
  • Deteriorates rapidly on storage
• Anti-P1 (P blood group) are IgM, naturally occurring P1 (-) individuals

  • Weak, cold-reactive saline agglutinin (4°C)
  • Some are reactive at Room temperature and binds complement at 37°C (detectable in AHG phase)
  • Associated with Fascioliasis, Clonorchis and Opisthorchis viverinii infection
• Anti-PP1 Pk (P blood group) is originally called as anti-Tja; first described on serum of Mrs. Jay (has p phenotype with adenocarcinoma of stomach)

  • Tumors contained P system Antigens and the Ab has cytotoxic properties that may have helped prevent metastatic growth post surgery
  • Produced by all p individuals without exposure
  • Reacts with all RBCs except from p individuals
  • Components are separable through adsorption
  • Have IgM and IgG component
  • Have a wide thermal range and binds complement (potent hemolysin)
  • Can cause HTR and HDN
  • Associated with spontaneous abortion in early pregnancy
• Alloanti-P are naturally occurring alloantibody in sera of all p k individuals

  • Reactivity is similar to anti-PP1 Pk (potent hemolysin)
  • Reacts with all RBCs except auto control and p phenotype
• Autoanti-P (P blood group) is associated with Paroxysmal Code Hemoglobinuria

  • Cold-reactive antibody
  • IgG with biophasic property
  • Binds RBCs in the cold (4°C) and causes hemolysis (complement activation) at 37°C
  • Demonstrated by Donath-Landsteiner test
• Paroxysmal nocturnal Hemoglobinuria is associated with acquired somatic mutations in a Pa gene resulting in deficiency in the key accelerating factor and MIRL protein in RBC leading to susceptibility to complement mediated lysis
• Paroxysmal code Hemoglobinuria is associated with the formation of autoantibodies that has an affinity in the P antigen and this autoantibody demonstrate biphasic property
• Biphasic property is when at 4°C, the autoantibodies binds to red blood, when warm temperatures, these bound antibodies will now cause hemolysis
• Autoanti-pk (P blood group) is seen in serum of individuals with biliary cirrhosis and AHA; inhibited by hydatid cyst fluid
• Tippett et al in 1965, described an antibody in serum of Hodgkin lymphoma patients, the Luke antigen
• I blood group system is discovered by Wiener et al in 1956

  • Only has 1 antigen
• I and i antigen (I blood group) are high incidence antigens (90% of the community has it)

  • Expressed in reciprocal relationship (developmentally regulated)
• Enzyme treatment of RBCs enhances I/i antigens
• • i antigen = predominant in fetal RBCs, decreases during the first 18 months of life
  • I antigen = increases until adult proportion are reached
• Anti-I (I blood group) are weak, naturally occurring IgM

  • Common autoantibody (particularly for those infected with Mycoplasma pneumoniae)
  • Testing at 4°C and enzyme treatment of RBCs may be required
  • Strong agglutination with adult RBCs and weak to no agglutination with cord RBCs(I blood group)
• Pathologic Anti-I (I blood group) is associated with cold agglutinin disease (strong IgM with broad thermal range of activity)

  • Can cause autoagglutination, vascular occlusion or hemolytic anemia
  • Production may be stimulated by Mycoplasma pneumoniae infection (I-like antigen)
  • Not associated with HDN
• Anti-i (I blood group) are cold reacting and rare; it produces strong reaction with cord RBCs and adult i RBCs

  • Weaker reactions with adult I RBCs
  • IgM, reacts best at 4°C, saline suspended cells
  • Associated with infectious mononucleosis, myeloid leukemia and alcoholic cirrhosis
• Anti-IT (I blood group) is IgM and frequently found in Melanesians and Yanomama Indians in Venezuela; associated with Hodgkin’s lymphoma
• Kell blood group system has 24 high and low incidence antigens; it is the first blood group system discovered after the introduction of AHG testing
• Anti-K (Kell blood group) is discovered from serum of Mrs. Kellager in 1946
• Levine et al in 1949, discovered anti-k, which has high incidence antithetical partner of K