MLSP 5513: Other Blood Groups of Interest

Lewis system

antigens formed in secretions and absorbed onto RBC surface

Kidd system

antibodies activate complement and titers drop quickly

Most red cell antigens are

immunogens and can elicit immune response

What are clinically significant antibodies classified as such

-decrease red cell survival

-transfusion reaction

-hemolytic disease of the fetus and newborn

Terminology: genes are

underlined or italicized

Terminology: allele letter

always superscript

Terminology: antibodies are described by

their antigen name with the prefix 'anti-'

The nomenclature has been standarized by

ISBT

ISBT blood group requirements

Consists of one or more antigens controlled at a single gene locus, or by two or more very closely linked homologous genes with little or no observable recombination between them

ISBT blood group collection

consists of serologically, biochemically, or genetically releated antigens, which do not fit the criteria required for system status

ISBT 700 series

contains antigens with an incidence of less than 1% and which cannot be included in a system or collection

ISBT 901 series

contains antigens with an incidence of greater than 90% and which cannot be included in a system or collection

Glycosyltransferases

-ABO

-H

-Lewis

-P

-I

Structural proteins

-Rh

-MNS

-Diego

-Gerbich

Transport proteins

-Rh

-Kidd

-Diego

-Colton

-Kx

Complement proteins

-Chido/Rogers

-Cromer

-Knops

Adhesion molecules

-Luthern

-Xg

-Indian

Biological receptors

-Duffy

-Knops

-Indian

Microbial receptors

-Duffy

-MNS

-P

-Lewis

-Cromer

How many genes interactions are involved with Le antigen formation

four separate loci

-ABO, H, Le and Se

-produces specific glycosyltransferases

ABO gene is located on

Chromosome 9

Where are the H, Se, and Le genes located

chromosome 19

Le encodes

alpha-4-L-fucosyltransferease

Se gene encodes

alpha-2-L-fucosyltransferases

Epithelial cells express

Type 1 precursor chain

Red blood cells express

Type 2 precursor chain

Secretor fucosyltransferase is responsible for

placement of a fucose sugar onto a Type 1 Precursor chain

-recongnizes beta 1-3

H fucosyltransferease places

a fucose onto type 2 prescursor chain

-recognizes the beta 1-4 linkage

The Lewis fucosyltransferase modifies

the type 1 prescurose chain to produce Lea and Leb

Lea antigen

-individuals without a functional Se gene

-Le(a+b-)

Leb antigen

-functional Se and Le genes

-Se fucosyltransferase will modify the Type 1 chain at the terminal galactose

-Le fucosyltransferase will also modify Type 1 at the GlcNAc residue

Le(a+b+) phenotype

-Se glycosyltransferase does not compete with Le glycosyltransferase

-common in asian population

Lewis antigens are not

alleles

Lewis antigen production requires

Se and Le genes

Se glycosyltransferase modifies

Type 1 precursor chain with fucose for production of A, B, H in secretions

Le glycosyltransferase modifies

Type 1 precursor chain with fucose to produce the Lea antigen or with Se glycosyltransferase (Leb antigen is formed)

Leb positive individuals must inherit both

Le and Se genes

Red blood cells will preferentially absorb

Leb over Lea from the plasma

Is the Se gene required for expression of Lea

No

Lewis antigens found in secretions are

glycoproteins

Lewis antigens that are found in plasma are

glycolipids

-absorbed onto the red cell surface

What is the source of the Lewis plasma glycolipids

GI tract

What kind of antibodies are the Lewis system

IgM

Which is more common Lea or Leb

Leb

Lewis (a+b-) phenotype

-occurs in a nonsecretor

-produces Beta1-4-fucosyltransferase

- fucose added to subterminal N-acetylglucosamine in the type 1 chain

-Lea substance absorbed onto red cells

-All are ABH nonsecretors

Lewis (a-b+) phenotype

-formed by interaction of Se and Lewis gene

-adds a second fucose to the subterminal N-acetylglucosamine

-Both Lea and Leb soluble antigens in secretions

-Only Leb absorbed onto RBCs from plasma

Lewis (a-b-) phenotype

-mutations in Le = non/partially functional transferase

-more common in blacks

-can be ABH secretors or nonsecretors

adults with Le are

Le(a-b+) or Le (a+b-)

ABH secretors with Le are

Le (a-b+)

ABH nonsecretors with Le are

Le(a+b-)

Individuals lacking two functional Le genes are

Le(a-b-)

Neborns: Lewis

-Lewis and ABH substances are in saliva at birth

-Lewis not detectable in plasma

-type Le (a-b-)

When is the Lewis substance detectable in plasma

after 10 days

Full Lewis phenotype expression occurs

6-7 years

Changes in Lewis antigens can occur

-pregnancy

-abnormal lipid metabolism

-antigens freely dissociate

Le(a-b-) individuals often make

anti-Lea and Leb

Which lewis antibody is more common and has a higher titer

Anti-Lea

When is anti-Leb produced

rarely by Le (a+b-)

Lewis antibodies characteristics

-naturally occurring

-usually IgM

When are antigen negative donors necessary when lewis antibodies are present

Antibody is reactive at 37C and hemolytic

Lewis group antibodies are frequently found in

sera of pregnant women

What enhances reactivity of lewis antibodies

enzymes

-can bind complement

-neutralized by lewis substances in saliva or plasma

Biological significance of Lewis System

-Leb antigen is a receptor for gram-neg bacteria

-loss of antigen associated with celiac disease

-may be an indicator in some tumors

-Le (a-b-) associated with coronary heart disease

-Lewis antibodies in Lewis negative renal transplant recipient -> higher rejection rates