Major Blood Group Systems Dependent on AHG

Question 1

What three blood group systems were discovered because of the IAT antiglobulin test

Answer 1

Kell
Duffy
Kidd

These are known as the ‘Big 3’
They are the most clinically significant after ABO and Rh

Question 2

When was the IAT discovered?

Answer 2

1946

Question 3

Why are Duffy, Kidd and Kell clinically significant?

Answer 3

They can all interact with complement

Duffy can also cause HDFN

Question 4

Disovery of the Kell Blood group system
(5)

Answer 4

First defining antigen of the Kell Blood Group was discovered in 1946 (same year as IAT) by an antibody in the serum of a Mrs Kelleher

It was discovered by Lancer; Coombs, Mourant and Race

It was found that she had an antibody which reacted with her husbands, her daughters and newborns red blood cells

Her antibody also reacted with 9% of a random population -> antibody against antigen called K (K1)

In 1949 (3 yrs later) the allelic partner/corresponding antigen k (K2) was discovered

Question 5

Origin of the Kell Blood group system
(5)

Answer 5

First defining antigen of the Kell Blood Group was discovered in 1946 (same year as IAT) by an antibody in the serum of a Mrs Kelleher

It was discovered by Lancer; Coombs, Mourant and Race

It was found that she had an antibody which reacted with her husbands, her daughters and newborns red blood cells

Her antibody also reacted with 9% of a random population -> antibody against antigen called K (K1)

In 1949 (3 yrs later) the allelic partner/corresponding antigen k (K2) was discovered

Question 6

When was the K antigen discovered, when was k discovered?

Answer 6

K was discovered in 1946 in a Mrs Kellaher by Lancet; Coombs, Mourant and Race

k was disocvered in 1949

Question 7

What are the four most common Kell antigens?

Answer 7

K (K1)
k (K2)
Kpa
Jsa

Question 8

What is an anti-k antibody known as and why?

Answer 8

This is known as Cellano as it was found in a Ms. Cellano

Question 9

Why is a Cellano difficult to work up and why?

Answer 9

An anti-k will usually cause a pan reactive panel

This is because 99.8% of the population are either Kk or kk
-> only 0.2% of people are KK => panreactive panel as we rarely get K- cells as part of our screen

It just means it can be more difficult to rule out other antibodies, might have to elute of anti-k etc etc

Question 10

What chromosome is Kell located on?

Answer 10

Chromosome 7

Question 11

Why did Ms Kellaher’s anti-K react with 9% of red cells?

Answer 11

This is because:
- 8.8% of people are Kk and 0.2% of people are KK

=> 9% of people have a K which her antibody would react against

Question 12

What is the percentage of each Kell phenotype?

Answer 12

91% are kk (K/Kell negative)
8.8% are Kk
0.2% are KK

Question 13

How immunogenic is K antigen?

Answer 13

1 in 10 produce an antibody if exposed to K antigen
-> since 90% of people are K- this can be seen

There are many reports of anti-K in transfused patients and multiparous women

Hence why women get K- blood in ireland

Question 14

How many antigens are there in the Kell system, why so many?

Answer 14

There are 27 antigens total

Due to multiple allelic system giving rise to antithetical antigens

There is actualy so many possible combinations that not all possible genotypes have been found yet e.g. Kpa and Jsa have occured on separate chromosomes in patient but never on the one gene

Question 15

What Kell antigens are found in nearly 100% of people?

Answer 15

k, Kpb and Jsb are found in nearly everyone

Question 16

What are the 11 Kell antigens you need to be concerned with?

Answer 16

K and k
Kpa, Kpb and Kpc (Kpa most common in caucasions)
Jsa and Jsb (Jsa in Blacks)
K11 and K17
K14 and K24

Question 17

What Kell phenotype will any Kpa+ be?

Answer 17

They will all be k+

i.e. Kpa+ only occurs in k+

Question 18

Why might it be that weve never recorded a Kpa and Jsa on the same chromosome?

Answer 18

This is because Kpa is predominantly found in whites (2.3% of caucasians)

While Jsa is found in predominantly blacks (20%)

Question 19

Other than Kpa and Jsa what is another Kell group antigen combination that has never been recorded, white might this be?

Answer 19

K and Kpa
Might be due to the realtively low frequency of both antigens
Only (9% of people have a K and only 2.3% of people have a Jsa)

Question 20

What is the Kell null state?

Answer 20

Ko

This is due to a lack of K gene or Kx gene (covalently bonded on rbc surface)

They produce an anti-Ku

Question 21

Describe the Kell glycoprotein, how does it express the antigens

Answer 21

A 93kD transmembrane, single-pass protein which carries the Kell antigens

It is an endothelin-3-converting enzyme

The Kell antigens are expressed in Low Desnity on the cell

Question 22

What is the function of Kell glycoprotein?
(3)

Answer 22

It is an endothelin-3-converting enzyme

It cleaves an inactive precursor called big-endothelin-3 to create active endothelin-3

This is a potent constrictor of blood vessels

Question 23

What kind of antigen is both Kell and Kx?

Answer 23

They are both glycoproteins (different though)

Kell is a single pass while Kx is a multipass (passes membrane 10 times)

Question 24

What treatments can affect Kell antigen expression?

Answer 24

Daratumumab and ZAP
-> No K expression after dara treatment - hence ehy typing is required before starting treatment

Question 25

What treatments can affect Kell antigen expression?

Answer 25

Daratumumab and ZAP
-> No K expression after dara treatment - hence ehy typing is required before starting treatment

Question 26

What method is in place to negate daratumumab interference?

Answer 26

Send sample to IBTS for DTT treatment -> negates DARA interference

Question 27

What chromosome is Kx antigen encoded on?

Answer 27

X chromosome - hence why its called Kx

Question 28

What chromosome is Kx antigen encoded on?

Answer 28

X chromosome - hence why its called Kx

Question 29

What can affect the Kell glycoprotein, how does this affect it?

Answer 29

Thiol degradation of double disulphide bonds (s-s-disulphide bonds)

These are needed for structural integrity

But this fact can be used in serologica investigations e.g. where there is an anti-K and an anti-Fya
-> it means we can remove Kell antigens if we need to investigate other antibodies

Question 30

What are three methods of thiol degradation that can be used on Kell antigens?

Answer 30

DTT
ZZAP
AET

Question 31

What are three methods of thiol degradation that can be used on Kell antigens?

Answer 31

DTT
ZZAP
AET

Question 32

When might thiol degradation of Kell be needed?

Answer 32

If we have an anti-k -> we rarely will have an anti-K well rarely have a K- cell to use in panel -> often pan reactive

To rule out any other antibodies we can treat the red cells with a thiol degradation method - we can then rerun the panel to check for other antibodies