In the Lewis System, there are 2 main antigens (Lea and Leb) which can lead to three common phenotypes: Le(a+b-), Le(a-b+), Le(a-b-)
Lewis antigens
in addition to RBC's they are found on platelets, endothelium, kidney, genitourinary, and gastrointestinal epithelium cells
Lewis antigens
lewis antigens are not synthesized by RBCs, but are passively absorbed onto the RBC membranes form a soluble Lewis glycolipid present in the plasma
Lewis antigen
it is though that the GI tract is the primary source of the LE glycolipid in plasma
Lewis antigens
these antigens are not intrinsic to the RBC membrane, so they can float off the red cells and stick to other plasma lipoproteins
for example, in pregnant women, there is an increase in plasma volume and a 4x increase in plasma lipoproteins. Because of this, they may appear Le(a-b-) transiently as the Le antigen is decreased on RBCs (diluted out)
Lewis antigens
Le antigen also decreases on stored red cells so Le phenotyping should be done sooner rather than later to avoid false negatives
biochemistry and synthesis of Lewis Antigens
antigen synthesis depends on the interaction of 2 distinct fucotransferases
the LE gene (FUT3)
the secretor gene (FUT2)
these enzymes fucosylate type 1 chains
FUT2 recognizes the type 1 chain precursor to form type 1 chain H substance
synthesis of Lewis antigen
FUT2 enables A,B, and H antigens to be secreted by coding for the production of the enzyme a1,2-fucose transferase
This adds a fucose to the type 1 chain forming H substance in secretions
synthesis of Lewis antigen
FUT3 is responsible for the presence of the LE antigens
the product of this gene is a transferase that adds a fucose to the residue as well
Lea
the Lea antigen is characterized by an a1-4-fucose attachement to the subterminal N-acetylglucosamine residue
Leb
The Leb antigen is determined by the same a1-4-fucose attachment to the subterminal N-acetylglucosamine residue with the addition of the H determinant - the a1,2-fucose attached to the terminal galactose residue
in secretors, this interaction occurs preferentially over Lea formation
Secretors
some precursor chains are not acted upon by the secretor transferase, but may accept a fucose from the Lewis transferase, forming Lea
Therefore, both Lea and Leb may be found in secretions but only Leb absorbs onto the red cells
anti-Lea
this is a common antibody that can be naturally occurring or immune stimulated
Le(a-b+) secrete Lea in their plasma and have a small amount on their RBCs - don't usually make anti-Lea
anti-Lea
will see anti-Lea with Le(a-b-) individuals (usually will see anti-Leb also)
most anti-Lea are clinically insignificant because they react at RT and not at 37 degrees
most are IgM, with some IgG
anti-Lea
does not cause HDFN because the antigen is a very low level on fetal cells
enzyme treated cells enhances the reaction
anti-Leb
this is not as common as anti-Lea
it may be seen in Le(a-b-) along with anti-Lea
it can be made by Le(a+b-) because they don't have Leb at all
it is typically IgM and RT reacting
enzyme treated cells enhances the reaction
I and i antigens
I and i are ubiquitous antigens on all cell membranes
their products are transferase enzymes that attach repeating units of Gal and GlcNAc to the ABO precursor substance
The I gene codes for branching of the precursor substance
Ii antigen structure
i antigen is linear
it is predominantly found on cord blood cells
I antigen is branched
we gradually convert from i to I during the first 18 months of life; not all i is converted to I, some i is still present on adult cells
Ii antigen structure
rare adult individuals termed iadult do not express I antigens on their RBCs
The I and i antigen sites are considered uncompleted ABHactive chains
When ABH are removed from the RBCs more I antigens are expressed (the I structure is located beneath the ABH antigens)
Ii antigens
I and i serve as substrates and scaffolds for the synthesis of ABH and other type 2 chain antigens
The i phenotype is characteristic of neonatal RBCs and maturing RBCs
can sometimes see increased i in people with chronic hemolytic disorders and stressed erythropoiesis
The I phenotype is common for mature RBCs in adults
as you age, I goes up and i goes down
anti-I
anti-I is common in the serum of healthy individuals, often occurs as anti-IH
it reacts with all adult cells, including the patient's own, all reagent cells, and all donor cells (strongest reaction with O and A2 cells)
it doesnt react with cord blood cells
Anti-I
anti-I is usually IgM and is a cold agglutinin (reacts best at 4-10 degrees C), reactions also are enhanced with albumin and enzyme treated RBCs
anti-I can interfere with ABO typing, antibody detection, and compatibility testing; need to avoid RT testing and use IgG specific AHG
Mycoplasma pneumoniae infection is a common cause of autoanti-I
anti-i
autoanti-i is an uncommon cold agglutinin
IgM antibody
weakly reactive at 4-10 degrees
most reactive with cord blood and iadult RBCs
anti-i
patient with infectious mononucleosis often have transient, but very potent, anti-i
autoanti-I and autoanti-i are significant in cold agglutinin syndrome (CAS) and mixed type autoimmune hemolytic anemia
P1PK antigens
these antigens are very similar to the ABO system antigens
includes P, P1, Pk, and P2
they are high prevalence antigens on the RBCs of nearly everyone, they are the most prevalent red cell glycolipid
P1PK antigens
P and Pk are also on lymphocytes, platelets, kidney, lung, heart, endothelium, placenta, and synovium cells
Pk is the precursor of all globo-seriesglycospoingolipids
there is a rare, null phenotype, p
P1 antigen
P1 consists of P1 and P antigens
75% of adults have P1 and it is mostly on RBCs
the strength of the antigen decreases during storage
it can also be found in secretions like plasma and hydatid cyst fluid (cyst of a tapeworm)
anti-P1
naturally occurring IgM
weak RT agglutinin
increases in patients with hydatid cyst disease, fascioliasis (liver fluke), and bird handlers
can see a combo antibody: anti-IP1
anti-P1
the antibody can be neutralized with hydatid cyst fluid of P1 substance derived from pigeon eggs; this helps when dealing with multiple antibodies
anti-P
anti-P is produced in individuals with paroxysmal cold hemoglobinuria (PCH)
in PCH IgGautoanti-P attaches complement whn cold (think fingers and toes); as the red cells circulate, they begin to lyse and release hgb
p Blood Types
p individuals can make anti-P1, anti-P2, and anti-Pk (anti-PP1Pk)
it is a potentnatural antibody and reacts with all red cells except for other p
predominantly IgM with some IgG
as very potent hemolysins, the antibodies are associated with HDFN and spontaneous abortions
p Blood types
the placenta is rich in P and Pk antigens, so it is a target for maternal antibodies
both p and Pk individuals need to get antigen negative blood for transfusion
Secretors
for secretors, only Leb will absorb onto red cells
this is probably because the higher concentration of Leb in the plasma allow Leb soluble antigen to compete more successfully for sites of absorption onto the red cell membrane
as a result, the red cells of these individuals always phenotypes as Le(a-b+) even though both Lea and Leb soluble antigens are present in the secretions and plasma
The combination of Lewis plus secretor status determines whether Lea or Leb is expressed on the RBCs and whether Lea or both Lea and Leb are expressed in the plasma and secretions
Since Le antigens are assembled in the plasma, if the Le gene is present some type of LE antigen will be present in the secretions and the plasma regardless of the secretor status
Lewis system - Secretor status determines which Lewis antigen is present
sese with Le: Lea is expressed (absorbed) on the RBCs and is present in plasma and secretions
Se (FUT2): if the secretor gene is present with Le, Leb is expressed on RBCs,a nd Lea and Leb are present in plasma and secretiosn
nonsecretor is Lewis A in secretions, secretor will have Lewis A and B in secretions, but only B in red cells
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lele: this genotype does not produce Lea or Leb regardless on the other genes present
red cells will have the phenotype Le(a-b-) and there are no Lewis antigens in the plasma or the secretions