THE MNS (002) SYSTEM

 The MNS blood group system has been assigned the ISBT number 002, second after ABO.
 4 important antigens
o M, N, S, s
o U (always present when S and s are inherited)

History
 Landsteiner and Levine immunized the rabbits with human RBCs, to find new antigen specificities.
o 1927: Anti-M and Anti-N was recovered from these rabbit sera
 M and N were antithetical antigens.
 1947: Walsh and Montgomery
o They discovered S which is a distinct antigen that is genetically linked to M and N
 1951: antithetical s was discovered
 There is a disequilibrium in the expression of S and s with M and N.
 Whites: Ns > Ms > MS > NS

Pic: the prevalence of the common MN and Ss phenotypes

 1953: Weiner
o He named U (antibody to a high prevalence antigen)
 Greenwalt and colleagues
o Observed that all U- RBCs were also S-s-resulted in the inclusion of U into the system
Notes:

 MNS system has 46 antigens, which is almost equal to Rh in size and complexity
 Genes encodes for MNS systems are located at chromosome 4
REMEMBER! MNS BLOOD GROUP SYSTEM HAS 46 ANTIGENS
M and N Antigens

 M and N antigens are found on glycophorin A (GPA)

 Glycophorin A
o Major RBC sialic acid (sialoglycoprotein, SGP); a rich glycoprotein

Pic:

 M and N differ in their amino acid residues at position 1 and 5

 M: defined by serine at position 1 and glycine at position 5
 N: leucine and glutamic acid at these positions

Note: antibody reactivity is dependent on adjacent carbohydrate chains which are rich in sialic acid

 about 106 copies of GPA/RBC

 M and N are easily destroyed because of the routine bb enzymes:
o Ficin
o Papain
o Bromelin
o Trypsin – less common
o Pronase – less common
 These antigens are also destroyed by ZZAP (DTT+ papain or ficin)
o They are not affected by DTT alone but also:
 2-aminoethylisothiouronium bromide (AET)
 α-chymotrypsin
 chloroquine
 glycine-acid EDTA treatment
 Treatment of RBCs with neuraminidase (cleaves sialic acid) or known as neuraminic acid/ NeuNAc
o Abolishes reactivity of some examples of abs.

S and s Antigens

 Located on smaller glycoprotein called glycophorin B (GPB)

 S and s are differentiated by amino acid at position 29 on GPB.
o Methionine: S
o Threonine: s
 GPB (about 200,000) fewer than GPA per RBC
o But, 1.5 times more copies of GPB on S+s- RBC than S-s+ RBCs.
 Less easily degraded by enzymes
  Ficin, papain, bromelin, pronase, and chymotrypsin can destroy S and s activity but the Amount of degradation
depends on:
o Strength of enzyme solution
o Length of treatment
o Enzyme to cell ratio
 Trypsin: doesn’t destroy S and s AGs. Neither DTT, AET, chloroquine, nor glycine-acid EDTA treatment.

Anti-M

 More common in children than in adults and common in patients with bacterial infection
 React best at pH 6.5
 Glucose dependent
 Naturally occurring saline agglutinins at RT testing (37 oC)
 Do not bind complement and doesn’t react with enzyme-treated RBCs
 Due to antigen doses:
o React stronger when homozygous, (M+N-) or (M-N+): genotype MM
o Weaker reactions occur when heterozygous state (M+N+): genotype MN
 Weak examples of the antibody can be enhanced by acidifying the serum, lowering the pH to 6.5
 Most are clinically INSIGNIFICANT. No HDFN or HTR
 Do not need to confirm donors are M negative, must be cross match compatible