MNS Blood Group System Flashcards
Compare frequency and clinical significance of MNSs antibodies
M and N are rarely clinically significant but more frequent
S and s are clinically significant but a lot less common
How many antigens are in the MNS blood group system?
46 antigens
How many antigens are in the MNS blood group system?
46 antigens
What does M and N code for versus S and s?
M and N encode a glycophorin A
S and s encode a glycophoin B
How frequent is glycophorin A vs glycophorin B?
Glycophorin A is expressed in millions
Glycophorin B only expressed in thousands
What is significant about the expression of glycophorin A
Glycophorin A can be used as a marker for red cells as it is only expressed on rbcs in circulation
- it is expressed on other cells outside of circulation
Coment on the MNS null state
Null state is very rare and has no affect on red cell health, this state does not produce antibodies in this state
Who discovered MNS and when, history of the blood group?
M and N first described by Karl Landsteiner and Philip Levine in 1927
They experimented by injecting rabbits - rabbit produced these antibodies
Remained a two allele system for 20 years until 1947 when S was defined by Walsh and Montgomery
Antithetical s was discovered in 1951 by Levine et al
What gene is MNS on, how are they expressed
Chromosome 4
Closely linked alleles - co dominantly expressed
Why is the MNS blood group system so complex?
Recombination between closely linked homologous genes GYPA and GYPB which encode GYPA and GYPB
How did GPB arise, how is GPB different from GPA
Duplication of GPA gene whereby exon 3 of GPB is spliced out
There are 7 exons in GPA, GPB is missing one of these
Instead GPB has a pseudoexon 3
What kind of proteins are GPA and GPB?
They are integral membrane proteins with a single transmembrane alpha-helical segment and with the N-termini located extracellular
How many copies of GPA vs GPB are found on a cell?
About 1x10^6 copies of GPA per red cell
About 20,000 copies of GPB per red cell
How does M and N differ from each other?
There are differences at two positions (1 and 5)
M: Ser1 + Gly5
N: Leu1 + Glu5
How does S differ from s?
There is a single amino acid different
S to s: Methionine to threonine
NB - same mismatch as occurs in K and k
What is another antigen of the MNS system other than M, N, S and s?
The U antigen
When was the U antigen discovered and by who?
Discovered by Weiner in 1953 when its antibody was implicated in a case of HDFN
What is the U anitgen, where is it found?
U is a high frequency antigen
Its shown to be on GPB along with the s antigens
Why are there many rare and unusua lantigens recognised and included in the MNS system?
Due to either hybrid GPA/GPB structures, glycosylation changes or amino acid substritutin
-> lots of different reasons for variation in antigens
Talk a little about the M and N antigens
They are caried by GPA
They are located at the N-terminus of GPA
They are easily destroed by routine BT enzymes
M and N are antithetical and polymorphic
Difference in position 1 and 5:
- = serine and glycine
- N = leucine and glutamic acid
They are not detected on lymphocytes, monocytes or granulocytes
GPA M and N have been detected on renal capillary endothelium and epithelium
Talk a little about the M and N antigens
They are caried by GPA
They are located at the N-terminus of GPA
They are easily destroed by routine BT enzymes
M and N are antithetical and polymorphic
Difference in position 1 and 5:
- = serine and glycine
- N = leucine and glutamic acid
They are not detected on lymphocytes, monocytes or granulocytes
GPA M and N have been detected on renal capillary endothelium and epithelium
Other than on red cells where are M and N found?
They are found on renal capillary endothelium and epithelium
Talk about S and s antigens
They are found on GPB
A meth29threonine polymorphism is responsible for S and s
S and s are less easily degraded by enzymes
S and s are not found on platelets, lymphoytes, monocytes and granulocytes
Why are S and s antigens less easily degraded by enzymes?
Because the antigens are located farther down the glycoprotein and enzyme sensitive sites are less accessible
Where is the U antigen located on GPB?
the U epitope is adjacent to the ponit where GPB enters into the lipid bilayer ie. between AA 33 and 39
Hence why only some enzymes work on U antigen
Why is anti-N so rare?
This is becase N is found on both S and s of GPB
=> to be N- you must also be both S- and s- which is really rare
Comment on the frequencies of MN haplotypes
28% = MM
50% = MN
22% = NN
What are the Ss hapotype frequencies (in caucasians)
SS = 11%
Ss = 44%
ss = 45%
What are the MNSsU frequencies in caucasians?
M+ = 78%
N+ = 72%
S+ = 55%
s+ = 89%
U+ = 99.9%
What are the MNSsU frequencies in blacks?
M+ = 74%
N+ = 75%
S+ = 31%
s+ = 93%
U+ = 99%
What percentage of people are U-?
1% of the world
- High enough percentage
- very difficult to get blood for these individuals
0.1% of caucasions and 1% of Blacks
How should you crossmatch blood for anti-M or anti-N?
If an anti-M or N is coming up at room temperature then you must get M-/N- units
If the anti-M or N is not coming up at 37 degrees then you just need crossmatch negative units
Most labs will just get M- unit (about 2 in 10 will be M-)
What is linkage disequilibrium give an example for MNS
This is where the antigens encoded by haplotypes occur in the population with a different prevalence than would be expected if the genes were not linked
If M and S were not linked the expected prevalence of M and S antigens in the population would by 17% according to frequency calculations
However it is observed from testing that the MS haplotype actually occurs in 24% of people as individuals who are M+ tend to be S+ as well
What is anti-M?
Anti-M os typically a cold agglutinin
It can be IgM or IgG
It is rarely involved in HTR or HDFN
It is often naturally occruring
It doesnt bind complement
Clinically significant anti-M is usually IgG and reactive at 37 degrees
It reacts best at pH 6.5
What is the preferred pH of anti-M, why is this significant
Preferred pH is 6.5
Anticoagulants used in blood make plasma slightly acidic
for this reason an anti-M might be detectable in a plasma sample but not serum
What is the preferred pH of anti-M, why is this significant
Preferred pH is 6.5
Anticoagulants used in blood make plasma slightly acidic
for this reason an anti-M might be detectable in a plasma sample but not serum
Talk about anti-N
Anti-N is rare
It is often a cold reactive IgM or IgG saline agglutinin that does not bind complement
It rarely causes HTR or HDN
It can demonstrate dosage
It is not clinically significant unless reactive at 37 degrees
IgG anti-N is rare and only found in M+N-S-s-U- individuals
What is the ‘N’ antigen compare to N?
An N antigen is present in a person who is N+
An ‘N’ antigen (pseudo-N) is present in someone who is M+N-S+s+ i.e. an N- individual who still has S/s
These individuals effectively still have an N antigen
This pseudo-N is slightly different in terms of phosphorylation and glycosylation but its presence means you wont produce an anti-N
What is the most potent anti-N?
IgG anti-N in someone who is truly N-
i.e. M+N-S-s-U-
Talk about anti-S and anti-s and anti-U
These are rarer but clinically significant antibodies
Usually IgG and reactive at 37 degrees in IAT
frequency: Anti-S, anti-s, anti-U (in order of discovery)
What should you do if you have a pan reactive anti-U patient who needs blood?
Give out ABO and Rh compatible units -> this is all your going to be able to do as we dont have U- blood in ireland, it will have to be imported
If you have anti-M and anti-N antisera you can use these to type the patient -> if both of these are negative you can assume patient is infact U- and doesnt have some other high frequence alloantibody
Compare M and N antibodies vs S, s and U
Anti-M and -N:
- Naturally occurring
- Cold IgM
- Dosage
- Clinically insignificant
Anti-S, -s, and -U
- Exposure is required
- Warm IgG
- Minimal dosage
- Clinically significant
How many rare units did the IBTS have to import in 2022?
9 units were imported for two patients
- 7 U- units (for a pregnant woman, she didnt use any)
- 2 Kpb- units
Why does anti-M tend to be cold reactive, why is anti-RhD not
The gap between M antigens on different cells is approximately 13.9nm, this is just within the range of IgG agglutinating span of 14nm i.e. anti-IgM is able to agglutinate cells on their own - need no outside help
The RhD antigen is very small compared to MN, this means there is a larger gap between cells, IgG cannot fill this gap => cells can be sensitised but wont agglutinate without addition of AHG to bridge molecules
Other than naturally occuring how might an anti-N occur?
Formaldehyde anti-N might occur in renal dialysis patients but its again not clinically significant it just causes interference
Its caused by washing dialysis equipment in formaldehyde
What is our plant lectin soure of anti-N?
Vicia graminea
- plant based antibody
What are three examples of other MNS antigens
T and Tn antigens
Mur antigen
What are T and Tn antigens
These are antigens which are only exposed with childhood infection of pneumococcal diseases
Neuraminidase cuts of sugars to expose these antigens known as crypt antigens
Everyone has antibodies against these antigens as they should normally be covered
How frequent is the Mur Antigen?
Its rare in White/Blacks
It occurs in 7% of Chinese
it occurs in 10% of Thai population
How does T antigen activation occur
Neuraminidase cuts of sialic acid groups of sugars to unmask the T antigens
This is a rare complication in paediatric patients
Occurs with severe pneumococcal infection
What are some complications that can arise with T antigens
All dnor plasma products will contain anti-T/Tn
- T and Tn antigens should never be exposed so everyone will express antibodies against them
If these paeds are transfused with either plasma or platelets their haemoglobin will decerase
Newborns with this condition are often given albumin when they present to clinic, albumin has high levels of T and Tn antiobdies -> paeds will experience haemolysis due to anti-T antibodies in albumin
What are hybrid molecules and how do hybird molecules occur
They are molecules containing portions of both GPA and GPB
They occur due to the presence of genes arising by duplication and location next to each other, leading to uneqal crossing over or gene conversion
They are grouped into low and high incidence antigens
This phenomenom is partly responsible for the 49 MNS antigens and many of the Miltenberger (Mi) variants
What is GP Mur?
GP Mur is mostly GPB with some GPA
Anti-Mr can cause HTR and HDFN
It is the most common blood group antibody after ABO in Hong Kong and Taiwan
- 7% of Chinese Mur+
- 10% of Thai are Mur+
What are the two GPA/GPB deficient phenotypes
U phenotype - GPB deficient
En(a-) phenotype - GPA deficient
What is U phenotype?
U is a high incidence antibody found on all RBCs except 1% of Black Americans (and 0.1% of whites)
U- individuals lack GPB because of a partial or complete deletion
They are usually S-s- U-
U antigen is resistant to enzyme treatment
What is the En(a-) phenotype?
ENA is a high incidence antigen
ENA negative (EN(a-)) results from homozygosity for a gene deletion at the GYPA locus
No GPA is produced ut GPB is not affected
What is the MNS null state, how does it occur?
Mk phenotype
The Mk gene represents a single, near complete deletion of both GYPA and GYPB:
M-N-S-s-U-
How does MNS null (Mk) affect red cells?
The MNS null state is not associated with RBC membrane defects
MkMk genotype is associated with decreased RBC sialic acid content but increased glycosylation of RBC membrane bands 3 &4.1 -> compensation for loss of negative charged GPA and GPB
