LEWIS SYSTEM
- Lea substance is secreted regardless of the secretor status
-ISBT No.: 007
- ISBT Symbol: LE
- Antibody Class: IgM
- Only system that is not manufactured by the RBCs
- Lewis antigens are not synthesized by the RBCs but incorporated
into the RBC membrane structure
- Lewis antigens are produced by the tissue cells and secreted into
body fluids
- It is referred to as a system rather than as a blood group because
they are found primarily in the secretions and in plasma
- These antigens are then adsorbed onto the RBC membrane from
plasma, but they are not really an integral part of the membrane structure
- Lewis antigen production depends on the inheritance of Lewis genes and
Secretor genes
- Genetic interaction between Lewis and ABO genes also exists
because the amount of Lewis antigen detectable on the RBC is influenced by
the ABO genes inherited.
INHERITANCE
- Lewis genes is located in chromosome 19
- Lewis genes do not code for the production of Lewis antigens but rather
produce a glycosyltransferase (L-fucosyltransferase)
- L-fucosyltransferase add L-fucose to the basic precursor substance
* What basic precursor? Type 1 or Type 2?
- Lewis genes codes for alpha-4-L-fucosyltransferase, which transfers L-
fucose to Type 1 precursor substance (Beta 1-3 linkage)
- the structure formed is known as Lea soluble antigen
- it is then adsorbed onto the RBCs
- the no.1 carbon of L-fucose is attached to the no.4 carbon of N-
acetyl-D-glucosamine
Lewis (a+b-)
- therefore an individual can be a nonsecretor of ABH but still able
to secrete Lea soluble antigen. Lewis(a+b-)
- All Le(a+b-) are nonsecretors of ABH substances
* Lewis antigens in saliva are glycoproteins
* Lewis cell-bound antigens are glycolipids
- L-fucosyltransferase has not been detected in plasma or in RBC stroma
Lewis (a-b+)
- Sese, ABO, Hh and Lewis genes are intimately associated in the formation
of Leb soluble antigens
- Lea and Leb are not alleles
- Le(a-b+) is the result of the genetic interaction of Lele and Sese gene
* Leb soluble antigen represents the product of genetic interaction
between Le (FUT3) and Se (FUT2)
- Se gene codes for the production of alpha-2-L-fucosyltransferase, which
adds L-fucose to type 1 precursor substance in the terminal galactose
forming type 1 H substance
- Le gene codes for the production of alpha-4-L-fucosyltransferase, which
adds L-fucose to type 1 precursor substance in the number 4 carbon of N-
acetylglucosamine forming Leb soluble antigen
* some precursor chains are not acted on by the Se fucosyltransferase but
may accept L-fucose from the Lewis fucosyltransferase forming Lea.
- therefore, both Lea and Leb soluble antigens can be found in the
secretions.
- However, only Leb adsorbs onto the RBC from the plasma due to
high concentration of Leb antigen
- its phenotype is Le(a-b+), even though both Lea and Leb soluble antigen are
present in the secretions and plasma
Lewis(a-b-): Secretor/Nonsecretor P Blood Group System, Globoside Blood Group System, And Globoside
- it is not caused by the absence of the Lewis gene (FUT3) but rather by Blood Group Collection
specific point mutations in the Le gene
- these mutations will give rise to a non-functional or partially active - Four antigens in two blood group systems
Lewis transferase (Lew) causing the negative expression of the Lewis antigen - P1 – in P Blood Group System
on the RBC. - P – in Globoside Blood Group System
- in this case, Lewis antigen is absent only on the RBCs tested serologically - Pk and Luke (LKE) antigens – in Globoside Blood Collection
with the Lewis antisera, however, the Lewis antigen is present in the tissues
and secretions of the Le(a-b-) secretors * All these antigens are collectively referred to as the P system.

* Le(a-b-) nonsecretor express Type 1 precursor - P1 ISBT no.: 003

* Le(a-b-) secretor express H Type 1 substances plus ABH soluble antigens - symbol: P1
- Led substance is expressed by Le(a-b-) secretor - P Globoside Blood Group System ISBT no.: 028
- Type 1 H Led substance - symbol: GLOB
- Lec substance is expressed by Le(a-b-) nonsecretor k
- P and LKE Globoside Collection ISBT no.: 209
- Type 1 precursor substance - symbol: GLOB

Lewis Antibodies Phenotypes:

- generally produced by Le(a-b-) P1, P2, p, P1k, P2k
- naturally occurring * common phenotypes: P1 and P2
- generally in IgM class * rare phenotypes: p, P1k, P2k
- activates complement

*P antigens are structurally related to ABH antigens

- Antigens are formed by the action of glycosyltransferase

- Landsteiner and Levine

- they injected rabbits with human rbcs and produced an antibody,
initially called anti-P, that divided human rbcs into two groups : P+ and P-

- Levine
- described anti-Tja (anti-PP1Pk)
- common to P+ and P- cells, and it is made by P null individual
 - P blood group antigens are resistant to treatment with ficin and papain,
DTT, chloroquine, and glycine-acid EDTA.
NOTE: - Reactivity of the antibodies can be greatly enhanced by testing with
* anti-P – anti-P1 enzyme-treated rbcs.
* P+ - P1
* P- - P2 BIOCHEMISTRY AND GENETICS
* P null – p - RBC antigens of the P blood group exist as glycosphingolipids
- as with ABH, the antigens result from the sugars added sequentially to
- Matson et al precursor structures.
- described a new antigen, Pk - precursor substances oof ABH antigens, type 2H chains also carry P1
- expressed on all rbcs except those of the very rare null phenotype antigen
- it is not readily detected unless P is absent * genes responsible for the formation of the P1 and ABH antigens
are independent

P1: chromosome 22
Phenotypes: P: chromosome 3 (gene: B3GALNT1: 3-B-N-acetylgalactosaminyltransferase)
P1, P2, p, P1k, P2k Pk: chromosome 22 (4-a-galactosyltransferase) (Gb3 or Pk synthase)
* common phenotypes: P1 and P2
* rare phenotypes: p, P1k, P2k - Lactosylceramide (ceramide dihexose) is the precursor substance
- Pk is formed upod the addition of galactose
-
P1, describes rbcs that react with anti-P1 and anti-P - P antigen is formed upon the addition of N-acetylgalactosamine in
- P2, do not react with anti-P1 but do react with anti-P Pk antigen
* when rbcs are tested with anti-P1 only, results should be written * this explains why high frequency Pk antigen is not apparent on red
as P1+ or P1- or P1 cells.
* when P1- reacts with anti-P, P2 phenotype. * Pk antigen is less accessible to its antibody
- null phenotype (p) do not react with anti-P1, anti-P, or anti-Pk - P1 is formed upon the addition of Galactose in Paragloboside
- P1k reacts with anti- P1k and anti- Pk but not with anti-P. which is also a precursor substance for ABH, or p
- P2k reacts with anti- Pk but not with anti-P1 or anti-P
Phenotype Antigens Antibodies
NOTE: P1 P1, P None
- like ABH, P antigens are synthesized by sequential action of P2 P Anti-P1
glycosyltransferases, which adds sugars to precursor substance. p None Anti-P, anti-P1,(Anti-pk)
P1k P1, Pk Anti-P
- P1 precursor can be glycosylated to type 2H chains, which carry ABH
P2k Pk Anti-P , Anti-P1
antigens
P1 ANTIGEN - causing them as potent hemolysin
- found in fetal cell as early as 12 weeks, but weakens with gestational age - has the potential to cause HTR and HDN
*Young fetus is more strongly P+ than older fetus - IgG anti-P is a factor in associated with spontaneous abortion and
- poorly developed at birth and may take up to 7 years to be fully expressed early pregnancy
- deteriorates rapidly in storage
* when P1 antigen are used for typing old cells, false negative may
result ALLOANTI-P
- P1 and P2 are analogous with A1 and A2 - naturally occurring in all Pk individuals
- reactivity is similar to anti-Tja
NOTE: - clinically significant in transfusion
- P1-like antigen
-Has been found in plasma, pigeons droppings and turtledoves
(white eggs of turtledoves) AUTOANTI-P
- P1 substance - anti-P specificity is associated with the cold-reactive IgG autoantibody in
- soluble form found in hydatid cyst fluid, extracts of Lumbricoides patients with Paroxysmal Cold Hemoglobinuria
terristris, and Ascaris suum - antibody activity is biphasic
*antibody attaches to rbc in cold and lyse rbc as they are warm to
37’C via complement activation
ANTI-P1 ANTIBODY
- antibody class: IgM * DONATH-LANDSTEINER TEST
- naturally occurring alloantibody in the sera of all P2 individuals - confirm the diagnosis of PCH
- weak, cold reacting antibody (4’C) - 2 phase test: 37’C and Ice bath
- clinically insignificant
- prewarm technique is used to avoid carry agglutination from room
temperature activity ANTI-Pk
* used to determine if antibody is reactive at 37’C - isolated from examples of anti-PP1Pk by selective adsorption with P1 cells
- Providing of P+ units is acceptable if compatible at 37’C - reported in the serum of individual with biliary cirrhosis and AIHA
- activity can be inhibited by hydatid cyst fluid
ANTI-PP1Pk
- anti-Tja
- first described in the serum of Mrs. Jay, a p null individual with
adenocarcinoma
- components are separable
- antibody class: IgG and IgM
- react over a wide thermal range and binds complement
I BLOOD GROUP SYSTEM AUTOANTI-I
- ISBT number: 027 - production is stimulated by microorganisms carrying I-like antigen
- ISBT symbol: I - M. pneumonia, L. monocytogenes

I and i antigens ANTI-i

- expressed in reciprocal relationship that is developmentally related - most are IgM
- infants are rich in i and I is almost undetectable - IgG are associated with HDN
- during the first 18 months of life, quantity of i decreases as I - potent examples are associated with:
increases until adult is reached - Infectious mononucleosis
- adults are rich in I and trace amount of i - Lymphoproliferative disease
* there is no true I and i phenotypes - Myeloid Leukemia
- Rare adult i or I negative - best react at 4’C
- individuals who do not change their i status after birth

ANTI-I ANTIBODY
- common antibody that can be benign or pathologic
- demonstrate strong reactions with adult cells and weak reactions with
cord blood samples
- Not associated with HDN because the antigen is poorly expressed on infant
red cell
- antibody class: IgM

BENIGN ANTI-I
- found in the serum of many normal healthy individual
- not associated in invivo red cell destruction
- weak, naturally occurring
- antibody class: IgM
- usually reacts only at 4’C

PATHOLOGIC ANTI-I
- potent IgM agglutinins with higher titer
- broad thermal range of activity
- attach in vivo and cause autoagglutination and vascular occlusion or
intravascular hemolysis