Transcript Document

Lewis System
Mohammed Laqqan
Lewis Antigens
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Soluble antigens produced by tissues and found in body fluids
(plasma)
The Lewis antigens are NOT intrinsic to red cell membrane.
– They are produced in the plasma (Secretions) and adsorbed from
the plasma onto the red cell membranes.
Lewis substance
adheres to RBC
becoming an antigen
RBC
Le genes
Le substance
in plasma
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Lewis System: Genetics
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Le gene, similar to the ABO
system, codes for the
production of an enzyme.
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Enzyme adds Fucose to the sub
terminal GlcNAc on (H)
Precursor Substance to form
Lea Ag. This occurs ONLY in
SECRETIONS.
Lea Antigen
This attachment can
occur ONLY on a
Type 1 Chain. Why?
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Type 1 Chain:
#1 carbon of Gal is attached to the #3
carbon of GlcNAc. Lewis transferase
enzyme adds Fucose in an (14)
linkage to make Lea antigen. It can add
this fucose ONLY to the Type 1 chain.
Why?
Type 2 Chain:
#1 carbon of Gal is attached to the #4
carbon of GlcNAc.
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Le gene enzyme adds Fucose here:
Following the action of the
Le gene the Se & H gene
enzyme now adds a fucose
to the same precursor
substance in the
SECRETIONS resulting in
the formation of the
Leb antigen.
Leb Antigen
What Genes are necessary for the production of Leb Ag’s?
Le, H and Se genes. Remember, the Se gene codes for the
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presence of the H antigen in secretions!
Lewis inheritance
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Lewis system depends on Hh, Se, and Le genes
le, h, and se do not produce products
If the Le gene is inherited, Lea substance is produced
Le, H, and Se genes must ALL be inherited to convert Lea
to Leb. Examples:
–
–
–
–
Le, se, H
le, hh, se
Le, Se, H
le, H, Se
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
Le (a+b-)
Le (a-b-)
Le (a-b+)
Le (a-b-)
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Lewis inheritance
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b
Le and H genes in a secretor = Le antigen
a
Le and H genes in a nonsecretor = Le antigen
le is an amorph
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Lewis System: Antigens
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Presence of Lea antigens is dependant on the inheritance
of the Le gene.
Presence of Leb antigens is dependant on the inheritance
of the Le, H and Se genes.
All are necessary to produce Leb antigens.
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Lea
Lea
Lea
Lea
What Le antigens would be
present in the secretions and
on the RBC if you inherit the
following genes?
Lea
Lea
Lea
Lea
Lea
Lea
Lea
Le le, se/se & H
The Lewis red cell
phenotype is: Le (a+ b–)
Have Lea in secretions.
Lea
Lea
Lea
Lea
Lea
Lea
Lea
Lea
Lea
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Leb
Leb
Leb
What Le antigens
would be present in the
secretions and on the
RBC if you inherit the
following genes?
Leb
Leb
Lea
Leb
Leb
Leb
Leb
Leb
Leb
Leb
Lea
Le le , Se se & H
The Lewis red cell phenotype
would be Le (a– b+). Have
Lea and Leb in secretions.
Leb
Lea
Leb
Leb
Leb
Leb
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Lewis Phenotype Frequencies
Phenotype
Whites (%)
Blacks (%)
Le (a+ b–)
22
23
Le (a– b+)
72
55
Le (a– b–)
6
22
Le (a+ b+)
rare
rare
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Lewis System: Antigens
What is missing?
– Where is Le (a+b+)?
– Leb antigen preferentially adsorbs onto the red cell
membrane over Lea. Lea is still in the plasma but not
found on the red blood cells
Lewis antigens routinely adsorb onto and elute off of the
RBC membrane.
Cord blood: Le (a-b-)
–
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Lewis Antibodies
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Anti-Lea, Anti-Leb
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–
–
Most common Lewis
antibody encountered
Lewis antibodies are
neutralized by Lewis
substances.
Usually occur naturally
in those who are Le(a-b-)
Lewis Abs
Clinically
Significant
Seldom
Abs class
IgM
Thermal range
4 - 22
HDNB
No
Transfusion Reactions
Extravascular
Rare
Intravascular
Rare
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Lewis Antibodies
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Other phenotypes Rarely produce the antibody
May be detected soon after pregnancy because pregnant
women may temporarily become Le(a-b-)
No clinical significance…Why?
– Le antibodies in a patient can be neutralized by the Lewis
antigens in the donor’s plasma (cancel each other out)
– do not cause HDN because they do not cross placenta
(antigens not developed well in cord blood)
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