Lewis.ppt

lewis blood group system- key points

2. Lewis blood group system -History
•First two examples of anti-Lewis, later to be
called anti-Le
a
were described by Mourant
in 1946.
•Andresonfound an antibody, later to
become anti-Le
b
•Pioneering work in the 1950s of Morgan
and watkins and of Kabat.

3. Lewis blood group
•Often referred to as histo-blood group
antigensas they are ubiquitous stuctures
•The antigens are manufactured by tissue
cells and secreted into body fluids.
•An ‘adopted’ blood group system as
antigens are not intrinsic to the red cells,
introduced into the membrane from the
plasma

4. Numerical notation for
the Lewis, and Hh systems, and for Le
c
and Le
d
Lewis(system007) Hh (system 018) Collection 210
LE1 Le
a
H1 H210001 Le
c
LE2 Le
b
210002 Le
d
LE3 Le
ab
LE4 Le
bh
LE5 Ale
b
LE6 Ble
b

5. Lewis biosynthesis
•The Le gene product is an α1,4-L-
fucosyltransferase which catalyses the transfer of
L-fucose from GDP-fucose to the N-
acetylglucosamine of type 1 acceptor substrates:
–To type 1 precursor to form Le
a
–To type 1 H to form Le
b
–To type 1 A to form Ale
b
–And to type 1 B to form BLe
b

6. Some glycosyltransferase genes
and the enzymes
Locus Allele Transferase
FUT1(H) H α1,2-L-Fucosyltransferase
h None
FUT2(SE) Se α1,2-L-Fucosyltransferase
se None
FUT3(LE) Le α1,3/4-L-Fucsyltransferase
le
FUT4, FUT5,
FUT6, FUT7
α1,3-L-Fucosyltransferase
FUT8 α1,6-L-Fucosyltransferase

7. Biosynthesis of ABO, Hh and Lewis blood group antigens

8. ABH non-secretors
(se/se)
•No 1,2-
fucosyltransferase
•Type 1 precursor-
*
Type 1 H
•ABH secretors (Se
gene +)
•Produce Type 1 H
Le
a
antigen
red cells are Le (a+b-)
Le
b
antigen
Red cells are Le(a-b+)

9. Lea and Leb are not antithetical antigens
produced by alleles
Lea antigen
Le
b
Se
Le
a
Se
LeLe

10. LEWIS INHERITANCE
•The Le gene –located on chr. 19 linked to C3
complement locus.
•Two allele system, 3 genotype possibilities: LeLe,
Lele, lele
•Inheritance of at least one Le gene causes production
of Le
a
–Le_H_sese-Le_hhSe_ Le_hhsese
•Inheritance of at least 1 Le, 1 H, and 1 Se causes
production of Le
a
, then Le
b
–Le_H_Se_
•Le
a
and H are isomers; differ only in positionof the
fucose
•ABO and Lewis enzymes compete for same substance

11. LEWIS POPULATION FREQUENCIES
White Blacks Indians
Le(a+b-)22 23 37
Le(a-b+)72 55 68
Le(a-b-)6 22 ?

12. LEWIS Ag VARIATIONS
•Red cells from fetuses, cord samples, and neonates
are generally Le(a-b-)
•Infants may be transiently Le(a+b+)before
becoming Le(a+b-)
•Lewis-positive women may become transiently
Le(a-b-)during pregnancy
•Loss of Lewis Ag expression on RBCs, caused by
abnormal lipid metabolism, also seen in:
–Cancer
–Alcoholic cirrhosis
–Some infections

13. Other antigens-Le
c
, Le
d,
Le
x ,
Le
y
•Antigens on Le(a-b-) red cells from
–ABH nonsecretor-Le
c
–ABH secretor –Le
d
or type 1 H
•Le
x
( CD15) and Le
y-
the type 2 isomers of Le
a
and Le
b
, are not really blood group antigen
•An α1,3-L-fucosyltransferase catalyzes the
transfer of L-fucose from a nucleotide donor to c-3
of the subterminal N-acetylglucosamine of
–Type 2 precursor-Le
x
Type 2 A-ALe
y
–Type 2 H-Le
y
Type 2 B -BLe
y

14. Α1,4-fucosyl transferase activity
In various tissues and secretions:
–Kidney
–Gastric mucosa
–Submaxillary glands
–Ovarian cyst linings
–Saliva
–milk
–Amniotic fluid
Not been detectedin –serum, red cells,
lymphocytes, granulocytes, or platelts

15. LEWIS Ags: EXPRESSION
IN SECRETIONS AND RBCs
•Though the Se gene affects Lewis Ag expression,
it does notaffect Lewis Ag distribution in
secretions
•Genotype Secretion Ags RBC Ags
Le, Se, A/HLe
a
,Le
b
,A,HA,H, Le (a
-
b
+
)
lele, Se,A/HA,H A, H
Le, sese, A/HLe
a
A, H, Le
a
lele, sese, A/H none A,H
Le, sese, hh,ALe
a
O
h Le
a

16. LEWIS ANTIBODIES
•Produced by Le(a
-
b
-
) people
•Naturally occurring
•IgM (usually); cold reacting to
thermotolerant
•Activate complement (may cause in vivoor
in vitroRBC hemolysis)-slowly.
•Do not cross placenta or cause HDN
•React better with enzyme treated panel cells

17. LEWIS ANTIBODIES: ANTI-Le
a
•More frequently encountered than anti-Le
b
•Generally IgM; IgG formed by Lewis negative
people only after significant exposure to Lewis
Ags
•Most are detected in saline suspension at RT;
some require 37
o
C and AHG
•Binds C’; agglutination enhanced by using
enzyme treated cells
•May be neutralized with Lewis positive plasma or
saliva
•Individuals with Le (a-b+) do not develop anti-Le
a
(residual antigen Le
a
in secretions)

18. LEWIS ANTIBODIES: ANTI-Le
b
•2 types of Anti-Le
b
–Anti-Le
bL
reacts with all Le(a
-
b
+
) cells regardless of
ABO type
–Anti-Le
bH
reacts with Le(a
-
b
+
) cells of O or A
2type
(probably has specificity for a combination epitope
(Le
b
and H)
•Weaker reacting than anti-Le
a
•Usually IgM; does not activate C’ readily
•Produced by Lewis negative people and occasionally
by Le (a
+
b
-
) people
•May be neutralized by plasma
•Anti-Le
b
usually found along with Anti-Le
a

19. Factors contributing to clinical insignificance of
Lewis antibodies
•Neutralization of Le antibodies by Le
substances present in the plasma
•Loss of red cell Le antigen into the plasma
•Lack of reactivity at 37 C and AHG phase
•Generally IgM in nature and incapable of
crossing placenta
•Le antigens poorly developed in newborn
infants

20. CLINICAL SIGNIFICANCE
•No HDN
–Lewis Ags not yet adsorbed to newborns’ RBC
membranes
–Many Lewis Abs are pentameric IgM
•Transfusion reactions possible but rare
–Lewis Ags in donor plasma may neutralize
some of the recipient Lewis Abs
–Lewis Ags on donor cells may disassociate
•Le antigens may act as receptors for several
pathogenic bacteria-Helicobacter pylori

21. Lewis antigen expression
•Fucosidosis patients have enhanced expression of Lewis
antigen
•Loss of Le antigen expression may occur in
-Infectious mononucleosis complicated with immune
hemolysis
-In various form of cancers (pancreatic, gastric,
colorectal, bile duct, bladder)
-Alcoholic cirrhosis
-Alcoholic pancreatitis
-Severe renal disease
•CA 19-9 antigen (sialylated –Le
a
)marker to support dx of
colorectal, pancreatic, and gastric cancers