Other Blood Group Systems

Question 1

What are the four other most important blood group systems?

Answer 1

MNS
Kel
Duffy
Kidd

Question 2

Why are MNS, kel, Duffy and Kidd important blood groups?
(4)

Answer 2

All react at 37 degrees

All cause HDN

All have IgG

All cause transfusion reactions

Question 3

Who found the MNS Blood Group System?

Answer 3

Landsteiner and Levine

Question 4

How did Landsteiner and Levine find the MNS blood group system

Answer 4

Experiments with immunised rabbits

Remained a simple two allele M and N system for 20 years

Question 5

Who found the S antigen and when

Answer 5

In 1947 the S antigen was defined by a new antibody by Montgomery and Walsh

This was followed by the antithetical antigen-s in 1951 by Levine et al

Question 6

What do we know about the genetics of MNS?

Answer 6

Both sets of genes are closely linked on Chromosome 4

Question 7

Where is MNS expressed?
(3)

Answer 7

The antigens reside on the major redd cell Glycophorins - GPA and GPB

M and N are found on GPA

S and s are found on GPB

Question 8

How does M differ from N?

Answer 8

Differs by 2 amino acids

Question 9

How does S differ from s

Answer 9

A single amino acid change

Question 10

Why are MN and S considered the same blood group
(2)

Answer 10

Right beside each other genetically

Therefore they are probably the duplication of a single gene

Question 11

Comment about MN antibodies
(3)

Answer 11

Anti-M and anti-N are typical ‘cold agglutinins’

They are IgM

They rarely cause HTR or HDNB

Question 12

Comment about Anti-S or anti-s antibodies

Answer 12

Associated with HTR and HDN

Question 13

What does is mean if a patient is M+, N-, S+ and s+?

Answer 13

MM homozygous for Glycophorin A i.e. all Glycophorin A will be M type

Glycophorin B will be 50% S and 50% s

Question 14

Comment on MNS in serology

Answer 14

MNS antigens susceptible to enzyme degradation

Proteolytic enzymes used in blood group serology include Papain, Bromelin, Ficin and their main effect is to reduce the ‘repulsive forces between rbcs”

Question 15

Who found the Kell Blood Group System and when

Answer 15

Lancet, Coombs, Mourant and Race first defined the antigen in 1946 by an antibody in the serum of a Mrs. Kellacher

Question 16

Write about the Mrs. Kellacher serum antibody. (Kell antibody)

Answer 16

This antibody reacted with the red blood cells of her husband, a daughter and her newborn

Also reacted with 9% of a random population antigen called K (K1)

Question 17

When was the allelic partner of K1 found?

Answer 17

In 1949 it’s allelic partner and corresponding antigen-k (K2), discovered

Question 18

K and k antigens are antithetical, what does this mean?

Answer 18

Directly opposed or contrasted, mutually incompatible

Question 19

Write about the Kell Blood group
(6)

Answer 19

Antigens are expressed on a red cell bound glycoprotein

K and k are antithetical

Well developed at birth

The K antigen is very immunogenic (second to the D antigen) in stimulating antibody production)

Many examples of Anti-K are found in transfused persons and multiparous women

We give K- blood to all women of childbearing years

Question 20

Comment on the genetics of the Kell System

Answer 20

Genes located on chromosome 7

Need to have KK to produce anti-k -> only 0.2% of the population

99.8% of people have a k, 91% are kk and 8.8% are Kk

Question 21

What is a k person called

Answer 21

Cellano

Question 22

Write about anti Kell antibodies
(4)

Answer 22

Usually IgG in nature

Active at 37 degrees Celsius

Cause HTR and HDNB

Require the antiglobulin (Coombs) test for their demonstration in vitro

Question 23

What might cause anti-K production in non-transfused children?

Answer 23

Bacterial infections e.g. E. Coli and S. faecium

Question 24

What is the Duffy (Fy) Blood Group System?
(3)

Answer 24

Cytokine receptor

Duffy antigen cleans up cytokines

In biochemistry known as Duffy associated receptor for cytokines -> DARC

Question 25

How was the Duffy blood group discovered? (4)

Answer 25

In 1950 the antibody to Fya was seen in a multi-transfused haemophiliac - Mr. Duffy In 1951 the antithetical antibody and antigen was found - anti-Fyb In 1955 it was realised that many black populations lacked Duffy antigens (Fya-b-) There are also Fy3, 4, 5, 6, but these do not feature in routine transfusion testing - extremely rare

Question 26

Why do 75% of black populations lack Duffy antigens (2)

Answer 26

The duffy antigen is the site where malaria gets into red blood cells By natural selection those who lacked duffy where protected against malaria in high risk regions of Africa

Question 27

Comment of the genetics of Blood Group Systems (3)

Answer 27

Found on chromosome 1 First antigen to be mapped Single amino acid difference between Fya and Fyb

Question 28

Comment on the trends in Duffy antigen expression (5)

Answer 28

49% are Fy(a+, b+) 34% are Fy(a-, b+) 17% are Fy(a+, b-) Fy(a-, b-) is rare in white but high in black populations Most people who are sickle cell are Fy(a-, b-) Very few donations are Fy(a-, b-) which are needed for sickle cell transfusions

Question 29

Fy(a-b-) gives resistance against which malaria causing parasite (3)

Answer 29

Plasmodium knowlesi -> also P. vivax Invasion site for P. knowlesi is the Fy6 antigen Fy6 is absent on Fy(a-, b-) cells

Question 30

How does malaria interact with Duffy antigens

Answer 30

Antigens act as receptors for the merozoite to attach to the red blood cell

Question 31

Comment on the Duffy antigens (4)

Answer 31

Well developed at birth Destroyed by enzymes Fya and Fyb Codominant alleles

Question 31

Comment on the Duffy antigens (4)

Answer 31

Well developed at birth Destroyed by enzymes Fya and Fyb Codominant alleles

Question 32

Comment on Duffy antibodies (6)

Answer 32

Implicated with HTR and HDN (rare) IgG Sometimes complement dependent - activate the pathway to C3 stage Stimulated by transfusion or pregnancy (not common cause of NDFN) Don't react with enzyme-treated RBCs Require antiglobulin test for demonstrate invitro Antigen deterioration can cause subsequent detection problems in the lab

Question 33

How was the Kidd (Jk) blood group discovered? (3)

Answer 33

Discovered in 1951 as a result of HDN in the 6th child born to a Mrs. Kidd - Jka -> John Kidd in 1953 anti-Jkb found in a transfused reaction patient Kidd antibodies usually found in combination with other antibodies and are notorious for delayed, secondary, transfusion reactions i.e. found in reactive patients

Question 34

List the most common Kidd antigens in whites

Answer 34

50% = Jk (a+b+) 27% = Jk (a+b-) 23% = jk (a-b-) Double negative rare especially in polynesian

Question 35

What are the most common kidd antigens in blacks

Answer 35

51% = Jk (a+b-) 41% = Jk (a+b+) 8.8% = Jk (a-b-) Double negative very rare

Question 36

What exactly are the Kidd antigens?

Answer 36

Urea transporters

Question 37

Comment on the Kidd Antibodies (6)

Answer 37

Require the IAT for their demonstration in vitro Responsible for approximately 30% of DHTRs Antigen deterioration and/or dosage possible a contributing factor Enhanced by enzymes Partially IgM/IgG -> can activate complement to cause significant haemolysis HDN rare but Kidd antigens found on foetal cells at 11 weeks pregnant