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4.1 Transfusion and Transplant Immunology > MNS Blood Group System > Flashcards

MNS Blood Group System Flashcards

1
Q

Compare frequency and clinical significance of MNSs antibodies

A

M and N are rarely clinically significant but more frequent
S and s are clinically significant but a lot less common

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2
Q

How many antigens are in the MNS blood group system?

A

46 antigens

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3
Q

How many antigens are in the MNS blood group system?

A

46 antigens

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4
Q

What does M and N code for versus S and s?

A

M and N encode a glycophorin A
S and s encode a glycophoin B

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5
Q

How frequent is glycophorin A vs glycophorin B?

A

Glycophorin A is expressed in millions
Glycophorin B only expressed in thousands

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6
Q

What is significant about the expression of glycophorin A

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
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7
Q

Coment on the MNS null state

A

Null state is very rare and has no affect on red cell health, this state does not produce antibodies in this state

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8
Q

Who discovered MNS and when, history of the blood group?

A

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

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9
Q

What gene is MNS on, how are they expressed

A

Chromosome 4

Closely linked alleles - co dominantly expressed

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10
Q

Why is the MNS blood group system so complex?

A

Recombination between closely linked homologous genes GYPA and GYPB which encode GYPA and GYPB

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11
Q

How did GPB arise, how is GPB different from GPA

A

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

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12
Q

What kind of proteins are GPA and GPB?

A

They are integral membrane proteins with a single transmembrane alpha-helical segment and with the N-termini located extracellular

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13
Q

How many copies of GPA vs GPB are found on a cell?

A

About 1x10^6 copies of GPA per red cell

About 20,000 copies of GPB per red cell

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14
Q

How does M and N differ from each other?

A

There are differences at two positions (1 and 5)
M: Ser1 + Gly5
N: Leu1 + Glu5

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15
Q

How does S differ from s?

A

There is a single amino acid different
S to s: Methionine to threonine

NB - same mismatch as occurs in K and k

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16
Q

What is another antigen of the MNS system other than M, N, S and s?

A

The U antigen

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17
Q

When was the U antigen discovered and by who?

A

Discovered by Weiner in 1953 when its antibody was implicated in a case of HDFN

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18
Q

What is the U anitgen, where is it found?

A

U is a high frequency antigen

Its shown to be on GPB along with the s antigens

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19
Q

Why are there many rare and unusua lantigens recognised and included in the MNS system?

A

Due to either hybrid GPA/GPB structures, glycosylation changes or amino acid substritutin
-> lots of different reasons for variation in antigens

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20
Q

Talk a little about the M and N antigens

A

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

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21
Q

Talk a little about the M and N antigens

A

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

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22
Q

Other than on red cells where are M and N found?

A

They are found on renal capillary endothelium and epithelium

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23
Q

Talk about S and s antigens

A

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

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24
Q

Why are S and s antigens less easily degraded by enzymes?

A

Because the antigens are located farther down the glycoprotein and enzyme sensitive sites are less accessible

25
Q

Where is the U antigen located on GPB?

A

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

26
Q

Why is anti-N so rare?

A

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

27
Q

Comment on the frequencies of MN haplotypes

A

28% = MM
50% = MN
22% = NN

28
Q

What are the Ss hapotype frequencies (in caucasians)

A

SS = 11%
Ss = 44%
ss = 45%

29
Q

What are the MNSsU frequencies in caucasians?

A

M+ = 78%
N+ = 72%
S+ = 55%
s+ = 89%
U+ = 99.9%

30
Q

What are the MNSsU frequencies in blacks?

A

M+ = 74%
N+ = 75%
S+ = 31%
s+ = 93%
U+ = 99%

31
Q

What percentage of people are U-?

A

1% of the world
- High enough percentage
- very difficult to get blood for these individuals

0.1% of caucasions and 1% of Blacks

32
Q

How should you crossmatch blood for anti-M or anti-N?

A

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-)

33
Q

What is linkage disequilibrium give an example for MNS

A

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

34
Q

What is anti-M?

A

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

35
Q

What is the preferred pH of anti-M, why is this significant

A

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

36
Q

What is the preferred pH of anti-M, why is this significant

A

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

37
Q

Talk about anti-N

A

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

38
Q

What is the ‘N’ antigen compare to N?

A

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

39
Q

What is the most potent anti-N?

A

IgG anti-N in someone who is truly N-
i.e. M+N-S-s-U-

40
Q

Talk about anti-S and anti-s and anti-U

A

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)

41
Q

What should you do if you have a pan reactive anti-U patient who needs blood?

A

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

42
Q

Compare M and N antibodies vs S, s and U

A

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

43
Q

How many rare units did the IBTS have to import in 2022?

A

9 units were imported for two patients
- 7 U- units (for a pregnant woman, she didnt use any)
- 2 Kpb- units

44
Q

Why does anti-M tend to be cold reactive, why is anti-RhD not

A

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

45
Q

Other than naturally occuring how might an anti-N occur?

A

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

46
Q

What is our plant lectin soure of anti-N?

A

Vicia graminea
- plant based antibody

47
Q

What are three examples of other MNS antigens

A

T and Tn antigens
Mur antigen

48
Q

What are T and Tn antigens

A

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

49
Q

How frequent is the Mur Antigen?

A

Its rare in White/Blacks

It occurs in 7% of Chinese

it occurs in 10% of Thai population

50
Q

How does T antigen activation occur

A

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

51
Q

What are some complications that can arise with T antigens

A

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

52
Q

What are hybrid molecules and how do hybird molecules occur

A

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

53
Q

What is GP Mur?

A

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+

54
Q

What are the two GPA/GPB deficient phenotypes

A

U phenotype - GPB deficient

En(a-) phenotype - GPA deficient

55
Q

What is U phenotype?

A

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

56
Q

What is the En(a-) phenotype?

A

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

57
Q

What is the MNS null state, how does it occur?

A

Mk phenotype

The Mk gene represents a single, near complete deletion of both GYPA and GYPB:
M-N-S-s-U-

58
Q

How does MNS null (Mk) affect red cells?

A

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

4.1 Transfusion and Transplant Immunology (24 decks)

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