Lewis Blood Group Flashcards

1
Q

List the carbohydrate based red cell antigen systems

A

Lewis
Li
PIPk

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2
Q

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

A

They can cause problems with our reverse group reactions

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3
Q

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

A

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

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4
Q

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

A

Cord blood cells are Lea-b-

Lewis antigens are poorly developed at birth

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5
Q

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

A

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

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6
Q

Talk about the genetics behind the Lewis blood group system

A

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

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7
Q

What does the Le gene produce?

A

An alpha 1,4 fucosyltransferase known as FUT3

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8
Q

Talk about the le/le phenotype

A

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

They produce an inactive FUT3 enzyme

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9
Q

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

A

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

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10
Q

Exaplain how Se gene forms Leb?

A

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

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11
Q

What percentage of people are secretors?

A

75%

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12
Q

What are the phenotype posibilities of Le and Se

A

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

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13
Q

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

A

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

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14
Q

Frequencies of Le phenotypes in caucasians

A

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

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15
Q

Frequencies of Le phenotypes in Blacks

A

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

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16
Q

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

A

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

17
Q

Where does Le add FUC3 to make Lea

A

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

18
Q

Where does Se add FUT2 to become Leb

A

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

19
Q

What does the Se gene encode

A

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

20
Q

Talk about the variation in Lewis antibodies

A

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

21
Q

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

A

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

22
Q

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

A

Le(a-b+)

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

23
Q

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

A

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

24
Q

When might someone lose their lewis antigens

A

Pregnancy
Cancer
Alcoholic cirrhosis
Viral infections
Parasitic infections

25
Q

What happens to the lewis group in pregnancy

A

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

26
Q

Explain how lewis antigens can be lost

A

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

27
Q

Talk about the lewis antibodies

A

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

28
Q

Talk about the use of Lewis structures to neutralise Lewis antibodies

A

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

29
Q

What are the two categories of anti-Leb

A

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

30
Q

What is anti-LebH?

A

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

31
Q

What is anti-LebL?

A

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

32
Q

What diseases are associated with the Lewis group

A

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

33
Q

Talk about Leb and H in H. pylori

A

The mucosal surfce has receptors to which H pylori binds

The fucose in the Leb antigen is important ????