Lewis Blood Group

Question 1

List the carbohydrate based red cell antigen systems

Answer 1

Lewis
Li
PIPk

Question 2

When do carbohydrate based blood groups cause problems in the lab?

Answer 2

They can cause problems with our reverse group reactions

Question 3

What are the antigens of the Lewis system, what exactly are they, where are they found?

Answer 3

Lea and Leb

Antigens very similar to ABH antigens but are type 1 chain carbohydrate determinants only

They are plasma derived antigens -> not part of red cell themselves

They are found circulating in plasma bound to lipoproteins

They are adosrbed onto red cells

Question 4

When is Lea-b- blood really only seen and why is this?

Answer 4

Cord blood cells are Lea-b-

Lewis antigens are poorly developed at birth

Question 5

Lewis are type 1 chain determinants, what does this mean?

Answer 5

Type 1 chains end with a Gal B1-3 GlcNAc B1-R sequence

Type 2 chains end with a Gal B1-4 GlcNAc B1-R sequence

*Get Chat GPT to explain this

Question 6

Talk about the genetics behind the Lewis blood group system

Answer 6

Le locus is found on the short arm of chromosome 19

Only one gene even though there is two antigens
Le and le alleles
- Le gene codes for a trasferase enzyme
- le gene is a silent gene (amorph) i.e. lack of Le

Question 7

What does the Le gene produce?

Answer 7

An alpha 1,4 fucosyltransferase known as FUT3

Question 8

Talk about the le/le phenotype

Answer 8

These individuals are homozygous for a point mutation Trp68Arg in the Le gene

They produce an inactive FUT3 enzyme

Question 9

If there is only Le and le gene alleles how is there an Lea and an Leb?

Answer 9

Its based on the combined presence of the secretor gene
Lea = Le gene but no Se gene
Leb = Le gene with Se gene

Question 10

Exaplain how Se gene forms Leb?

Answer 10

Le gene encodes an FUT3
Se gene also encodes an FUT2

i.e. FUT3 added onto type 1 chain = Lea
-> FUT2 and FUT3 on type 1 chain = Leb

Question 11

What percentage of people are secretors?

Answer 11

75%

Question 12

What are the phenotype posibilities of Le and Se

Answer 12

Le gene = Le(a+b-)
Le gene + Se gene = Le (a-b+)
le gene +/- Se gene = Le(a-b-)

Question 13

In what phenotype is anti Lea and Leb seen, explain the significance

Answer 13

anti-Leb seen in any Le(a+b-) or Le(a-b-)

anti-Lea seen only in Le(a-b-)
-> this is because in Le(a-b+) only some of the Lea is converted into Leb i.e. there is still some Lea on cells, therefore no antibody produced against it

This means having to Lea and b type patients if query an anti-Lea - cant just lea type them

Question 14

Frequencies of Le phenotypes in caucasians

Answer 14

Le(a+b+) = rare
Le(a+b-) = 22%
Le(a-b+) = 72% -> think about roughly 75% being Se+
Le(a-b-) = 6%

Question 15

Frequencies of Le phenotypes in Blacks

Answer 15

Le(a+b+) = rare
Le(a+b-) = 23
Le(a-b+) = 55%
Le(a-b-) = 22%

Question 16

Why is Le(a+b+) so rare?

Answer 16

This is because Leb antigen is preerentially adsorbed onto the red cell membran over Lea

Lea will still be present in the plasma but wont be found on red cells

Hence why patients are red cell typed as Lea- but wont produce an anti-Lea

There is usually a very small undetectable amount of Lea on the red cells

Question 17

Where does Le add FUC3 to make Lea

Answer 17

To the sub terminal GlcNAc on the ABH system precursor subst to form the Lea antigen

This happens in secretions not on the red cell surface

Question 18

Where does Se add FUT2 to become Leb

Answer 18

Following action of Le of adding FUT3 to form Lea

The Se gene adds FUT2 to the same polysaccharide resulting in Leb formation

This only happens in secretions not on rbc

Question 19

What does the Se gene encode

Answer 19

Encodes the presence of the H antign in secretions
encodes a FUT2

Question 20

Talk about the variation in Lewis antibodies

Answer 20

Varying stregth of antibodies depending on blood group
e.g. person might have an anti-Lea highly specific to Lea on group A red cells
-> antibodies with sligtly different specificities to the same chain -> blood group antigens just add on differet sugars to the same basic H antigen structure as with Le

Question 21

What would you expect from the phenotype Lele and se/se?

Answer 21

Le(a+b-)
Lea in secretions and therefore adsorbed on red cells

Question 22

What would you expect from the phenotype Lele and Se/se?

Answer 22

Le(a-b+)

Lea and Leb in secretions but vast majority of Leb on red cell

Question 23

What is the most significant characteristic of Lewis antigens and antibodies?

Answer 23

People can loose their lewis antigens
Transient anti-Le antibodies - can come and go

Question 24

When might someone lose their lewis antigens

Answer 24

Pregnancy
Cancer
Alcoholic cirrhosis
Viral infections
Parasitic infections

Question 25

What happens to the lewis group in pregnancy

Answer 25

Many pregnant lose their lewis antigens and gain transient lewis antibodies Type and antibodies return to normal after delivery

Question 26

Explain how lewis antigens can be lost

Answer 26

Lewis antigens are found in plasma attached to lipoproteins In pregancy or infection there is an increase in lipoproteins This dilutes out antigens on the red cells results in loss of antigens and thus production of antibodies

Question 27

Talk about the lewis antibodies

Answer 27

IgM Enhanced reactivity with enzyme treated cells Good complement activators -> in vivo haemolysis Often causes weak/dirty looking agglutination Can be neutralised by Lewis substances Lea is much more common - think of frequency of Se

Question 28

Talk about the use of Lewis structures to neutralise Lewis antibodies

Answer 28

This is also what is done for query Chido-Rodgers - anti-chido against C4 - incubate query chido plasma with anyones red cells (almost everyone has C4) - antibody removed from plasma - removed reactivity - can now investigate plasma for other alloantibodies Same for Lewis eexcept selecting cells a little more complicated due to different antibodies etc

Question 29

What are the two categories of anti-Leb

Answer 29

Anti-Le(bH) Anti-Le(bL)

Question 30

What is anti-LebH?

Answer 30

Antibody that reacts best with Leb positive red cells with the highest amount of H antigen i.e group O or A2 Leb positive red blood cells More common then LebL

Question 31

What is anti-LebL?

Answer 31

An anti-Leb which reacts equally with the Leb antigen on red cells of all ABO phenotypes

Question 32

What diseases are associated with the Lewis group

Answer 32

Lea and H antigen are the receptor site for H. pylori Le(a-b-) associated with increased E. coli and candida infections - unknown why this is the case Le(b) and Type 1 H are receptors for Norwalk virus which causes acute gastroenteritis

Question 33

Talk about Leb and H in H. pylori

Answer 33

The mucosal surfce has receptors to which H pylori binds The fucose in the Leb antigen is important ????