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Historical Background

Landsteiner and Levine (1927)

- began immunizing rabbits with human RBCs. Among the antibodies recovered from
this rabbit sera were anti-M and anti-N (antithetical antigens)
Walsh and Montgomery(1947)
- discovered S, a distinct antigen that appered to be genetically linked to M and N .
Its antithetical partner s was discovered in 1951
Weiner (1953)
- he named antibody to a high-prevalence antigen U. The observation by Greenwalt
and colleagues that all U-RBCs were S-s resulted in the conclusion of U into the
46 antigens have been included in MNS system
The genes encoding the MNS antigens are located
on chromosome 4
MNS blood group system has been assigned the
ISBT number 002, second after ABO.
MN antigens

Found on well characterized glycoprotein called glycophorin A (GPA)

Differ in amino acid residue at position 1 and 5;
* M has serine at position 1 and glycine at position 5
*N has leucine and glutamic acid
The antibody reactivity may also be dependent on adjacent
carbohydrate chains , which are rich in sialic acid.
MN antigens

Well developed at birth

Easily removed or destroyed by enzymes ficin,papain and bromelin and
by less common enzymes trypsin and pronase.
The antigens are also destroyed by ZZAP
M and N antibodies are heterogeneous; some may recognized only
specific amino acids but others recognize both amino acids and
carbohydrate chains.
Ss antigens

Located on smaller glycoprotein called glycophorin B (GPB)

Differentiated by the amino acid at position 29 on GPB.
* S has Methionine
* s has Threonine
The epitope may also include the amino acid residues at position 34 and
35 and the carbohydrate chain attached to threonine at position 25.
Fewer copies of GPB than GPA per RBC.
There are about 1.5 times more copies of GPB on S+s- RBCs tnan on S-
s+ RBCs.
Ss antigens

Well developed at birth

Less easily degraded by enzymes
Ficin , papain, bromelin, pronase and chymotrypsin can destroy S and s
activity but, the amount of degradation may depend on:
* Strength of the enzyme solution
* Length of treatment
* Enyme-to-cell ratio
Trypsin does not destroy Ss antigens.

Most examples are naturally occurring , cold reactive saline agglutinins

that reacts below 37C.
IgM or IgG antibody
Usually do not bind complement .
Do not react with enzyme-treated RBCs.
Appears to be more common in children than in adults .
Particularly common in patients with bacterial infections.
Rarely causes HTRs, decreased red cell survival and HDFN

May react better with M+N- RBCs (genotype MM) than

with M+N- (genotype MN)
Very weak anti-M may not react with M+N+ at all.
Antibody reactivity can be enhanced by increasing the serum-to-cell
ratio or incubation time, or both, by decreasing incubation temperature
or by adding potentiating medium.
Some examples are pH dependent reacting best at pH 6.5
Other examples react only with red cells exposed to glucose solutions.
Anti- N

Cold reactive IgM or IgG saline agglutinin that does not bind complement or
react with enzyme-treated RBCs.
Can demonstrate dosage reacting better with M+N- (NN) RBCs than witn
M+N+ (MN) RBCs.
Rare examples are pH- or glucose- dependent.
Not clinically significant unless it reacts at 37C.
Implicated only with rare cases of HDFN.
Less common than anti-M.
Seen in renal patients, who are dialyzed on equipment sterilized with
Anti-S and Anti-s

Most examples are IgG reactive at 37C and the antiglobulin test phase.
Implicated with severe HTRs with hemoglobinuria and HDFN.
More likely to be clinically significant and may bind complement.
It can be difficult to provide blood for a patient with anti-s because only
11% of whites and 3% of blacks are s. Compared with S that is much
easier to find, whites has 45% and blacks has 69% of S.
GPA- and GPB- Deficient phenotypes

A. U-phenotype
-U for universal
-Antigen is located on GPB very close to the RBC membrane between
amino acids 33 and 39
-High prevalence antigen is found on RBCs of individuals except about
1% of African Americans ( and 1 to 35% of Africans) who lack GPB.
- In S-s-U- individuals , complete loss or recombination of GPB occurs,
leading to altered expression of S/s and U antigens.
-Anti-U is rare but can be formed in S-s- individuals; typically IgG and can
also cause HDFN and HTRs. It is enhanced with enzyme treatment.
GPA- and GPB- Deficient phenotypes

B. En(a) Phenotype
Darnborough and Furuhjelm(1969)described an antibody to the same
high prevalence antigen called Ena(for envelope)
Most En(a) individuals produce anti-Ena
Anti-EnaTS recognizes a trypsin-sensitive(TS) area on GPA between
amino acids 20 and 39
Anti-EnaFS reacts with a ficin sensitive (FS) area betweemn amino acids
46 and 56.
Anti-EnaFR reacts with a ficin resistant (FR) area around amino acids 62
and 72.
GPA- and GPB- Deficient phenotypes

C. Mk phenotype
Named by Metaxas and Metaxas-Buhler (1964) when they found an allele that
did not produce M or N.
Lacks all MNS antiges including En(a) as a result of recombination and deletion
of glycophorins A and B .
In 1979 two related MkMk blood donors were found, the RBCs of these
individuals typed M-N-S-s-U-En(a-)Wr(a-b-) but they had normal hematologic
Mk genes represents a single , near complete deletion of both GYPA and GYPB
MkMk genotype is associated with decreased RBC sialic acid content but
increased glycosylation of RBC membrane bands 3 and 4.1.
Other antibodies

Antibodies to high-prevalence antigens

- easily detected with antibody detection RBCs.
Antibodies to low-prevalence antigens
-rarely detected by antibody detectection test but are seen us
unexpected incompatible crossmatch or an unexplained case of HDFN
Disease association

GPAM may serve as the receptor by which certain pyelonephritis strains

of E. coli gain entry to the urinary tract.
Plasmodium falciparum appears to use alternative receptors including
GPA and GPB for cell invation.