Lewis Blood Group Flashcards
List the carbohydrate based red cell antigen systems
Lewis
Li
PIPk
When do carbohydrate based blood groups cause problems in the lab?
They can cause problems with our reverse group reactions
What are the antigens of the Lewis system, what exactly are they, where are they found?
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
When is Lea-b- blood really only seen and why is this?
Cord blood cells are Lea-b-
Lewis antigens are poorly developed at birth
Lewis are type 1 chain determinants, what does this mean?
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
Talk about the genetics behind the Lewis blood group system
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
What does the Le gene produce?
An alpha 1,4 fucosyltransferase known as FUT3
Talk about the le/le phenotype
These individuals are homozygous for a point mutation Trp68Arg in the Le gene
They produce an inactive FUT3 enzyme
If there is only Le and le gene alleles how is there an Lea and an Leb?
Its based on the combined presence of the secretor gene
Lea = Le gene but no Se gene
Leb = Le gene with Se gene
Exaplain how Se gene forms Leb?
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
What percentage of people are secretors?
75%
What are the phenotype posibilities of Le and Se
Le gene = Le(a+b-)
Le gene + Se gene = Le (a-b+)
le gene +/- Se gene = Le(a-b-)
In what phenotype is anti Lea and Leb seen, explain the significance
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
Frequencies of Le phenotypes in caucasians
Le(a+b+) = rare
Le(a+b-) = 22%
Le(a-b+) = 72% -> think about roughly 75% being Se+
Le(a-b-) = 6%
Frequencies of Le phenotypes in Blacks
Le(a+b+) = rare
Le(a+b-) = 23
Le(a-b+) = 55%
Le(a-b-) = 22%
Why is Le(a+b+) so rare?
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
Where does Le add FUC3 to make Lea
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
Where does Se add FUT2 to become Leb
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
What does the Se gene encode
Encodes the presence of the H antign in secretions
encodes a FUT2
Talk about the variation in Lewis antibodies
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
What would you expect from the phenotype Lele and se/se?
Le(a+b-)
Lea in secretions and therefore adsorbed on red cells
What would you expect from the phenotype Lele and Se/se?
Le(a-b+)
Lea and Leb in secretions but vast majority of Leb on red cell
What is the most significant characteristic of Lewis antigens and antibodies?
People can loose their lewis antigens
Transient anti-Le antibodies - can come and go
When might someone lose their lewis antigens
Pregnancy
Cancer
Alcoholic cirrhosis
Viral infections
Parasitic infections
What happens to the lewis group in pregnancy
Many pregnant lose their lewis antigens and gain transient lewis antibodies
Type and antibodies return to normal after delivery
Explain how lewis antigens can be lost
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
Talk about the lewis antibodies
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
Talk about the use of Lewis structures to neutralise Lewis antibodies
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
What are the two categories of anti-Leb
Anti-Le(bH)
Anti-Le(bL)
What is anti-LebH?
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
What is anti-LebL?
An anti-Leb which reacts equally with the Leb antigen on red cells of all ABO phenotypes
What diseases are associated with the Lewis group
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
Talk about Leb and H in H. pylori
The mucosal surfce has receptors to which H pylori binds
The fucose in the Leb antigen is important ????
