Other Major Blood Group Systems Flashcards
Describe the unique characteristics of Lewis Antigens and where they are located? (3)
- Not intrinsic to RBCs
- Are on Type I glycosphingolipids
- Passiely adsorbed on to RBC membrane from plasma
Who made the first Lewis Antibody and When was it reported?
Mourant, 1946
Lea and Leb do not result from _______ _______. Rather from the interaction of two ____________ encoded by independed genes _____ and ______.
- alternative alleles
- fucosyltransferases
- Le and Se
Identify what type of chain Lewis antigens are?
Type I glycolipids
How are Lewis Antigens produced and where are they found?
By tissue cells and found primarily in in plasma and other body secretions.
NOT manufactured by RBCs
Idenify the chromosome the Se gene is located on?
Chromosome 19
What does the Se gene code for and what does it do?
It codes for a fucosyltransferase enzyme that adds L-fucose to Type I precursor chains.
What gene is similar to the Se gene and how is it similar, yet different?
H gene is similarly located on chromosome 19 and also codes for the same fucosyltransferase. HOWEVER the H gene adds L-fucose to the Type II precusor chain.
What are the Secretor phenotypes and what is the non-secretor phenotype?
- SeSe
- Sese
- sese (amorph)
What percentage of the population are secretors?
80%
What percentage of the population are non-secretors?
20%
What genes encode the enzymes FUT1, FUT2, FUT3?
- FUT1 = H gene
- FUT2 = Se gene
- FUT3 = Lewis gene
The Lewis gene is found on which chromosome?
19
What does the Le gene code for and what does it do?
Codes for alpha 1,4-L-fucosyltransferase (FUT3), which transfers L-fucose to the Type I precursor H chain forming Leb
If A and B genes are present along with Le what is the result?
Type I (1H) converted to A and B structures then Le fucosyltransferase will produce ALeb and BLeb
What is made is small amounts before the secretor enzyme adds terminal fucose?
Lea
Lewis Phenotypes: Describe Le (a+b-)
What genes are present?
What is present in secretions and why?
- Le and H genes present
- Lea produced
- No Se gene present as no Leb made so are nonsecretors
- Lea present in secretions beceause it is a type I chain
Lewis Phenotypes: Describe Le (a-b+)
What genes are present?
What is present in secretions and why?
- Genes Le, H and Se
- Se gene needed to make Leb
- Leb is made preferentially over Lea
- All are secretors (Se gene present) will have ABH Lea and Leb in secretions
Lewis Phenotypes: Describe Le (a-b-) Secretor and nonsecretors.
- No Le gene
- cannot make alpha 1,4 L-fucosyltransferase
- Le (a-b-) Secretors do not make Lea/b but have ABH Antigens in secretions
- Le (a-b-) nonsecretors lack Le and Se genes so NO ABH antigens present in secretions.
Which Lewis phenotype is 4 times more common in black than white?
Le(a-b-) Nonsecretors (lele)
Which Lewis Phenotype is insignificant an rare; with no secretions stated.
What results in this phenotype?
- Le (a+b+)
- Weak Se gene that produces a FUT2 that competes less effectivelt with Le fucosyltransferase (FUT3) resulting in the prescence of both Lewis Antigens.
What gene must be present for the formation of Leb?
Se gene
Are Lewis antigens well developed at birth?
No, but begin to appear shortly after because antigens are adsorbed on to RBC membrane
What Lewis phenotype is chord blood?
Le (a-b-)
When Le and sese genotypes are inerited, Lewis antigens are not detectabe on chord cells but infants secrete____ in their ______
- Lea
- Saliva
When are Lewis Antigens detectable in plasma after birth?
10 days
At what age will the true Lewis Phenotype show up?
How do the Lewis Phenotypes develop? (3)
6-7 years
- Le and Se
- Le (a-b-) –> Le(a+b-) –> Le(a-b+)
- Le and sese
- Le(a-b-) –> Le(a+b-) after 10 days
- lele and sese
- Le(a-b-) for life
T/F: Lewis antigens are readily shed from tansfused RBCs within a few days ofr transfusion?
True
What is the ISBT code for Lewis Antigens?
007
What is the ISBT # for Lea?
LE1
What is the ISBT # for Leb?
LE2
Identify the antibody and ISBT # of the Ab that reacts with Le(a+b-) and Le(a-b+) RBCs from adults and 90% of chord RBCs?
- Anti-Leab (reacts with Leab)
- LE3
What Ab reacts with Aleb and its ISBT #?
- Anti-Aleb reacts with groupA1 Le(b+) and A1B Le(b+)
- LE5
What Ab reacts with group O Le(b+) and A2 Le(b+)?
What is the ISBT #?
- Anti-LebH
- LE4
Identify the ISBT #s for Anti-ALeb and Anti-BLeb?
- LE5
- LE6
How does pregnancy affect Lewis antigens?
- Decline dramatically
- Transient Anti-Lea formed
- Physiologic changes affect the Lewis glycolipid distribution between plasma and RBCs
What is the most commonly encoutered Antibody of the Lewis system?
Anti-Lea
Which microorganism is of biological significance in the Lewis system and why?
- Helicobacter pylori - causes gastric and duodenal ulcers, mucosa-associated lymphiod tissue lymphoma, atrophic gastitis and ademocarcinoma.
- Lewis antigens have receptors that interact with microorganism.
Lewis antigens ar3e associate with what other disease factors?
- Peptic ulcers
- Ischemic heart disease
- cancer
- kidney transplant rejection
Who discovered the S antigen that was linked to M and N?
Walsh and Montgomery
Identify the protein that M and N antigens are found on?
GYP A (Glycophorin A), the major sialic acid-rich glycoprotein (sialoglycoprotein - SGP)
M and N are antithetical and differ in amino acid sequence. What is the different amino acid residues in position 1 and 5 for M and N
- M
- 1 - Serine
- 5 - glycine
- N
- 1 - Leucine
- 5 - glutamic acid
What are the different M and N phenotypes?
- M+N-
- M+N+
- M-N+
Which of the MNS system antigens are well developed at birth?
S and s
On what proteins are S and s antigens located?
GYP B (glycoprotein B)
Idenitfy the different amino acid residues between S and s antigens at position 29?
S - Methionine
s - Theronine
What are the S phenotypes of the MNS system?
- S+s-
- S+s+
- S-s+
- S-s-U-
Which MNS phenotype is seen almost exclusively in African Americans?
S-s-U-
What is the issue with the S-s-U- phenotype?
- Most people have the U antigen, so anti-U will react with the cells of most people (100% white & 99% black).
- Would need to consult the Rare Donor Registry
What results in the En(a-) Phenotype?
homozygous for rare gene deletion of GYPA locus so no GYPA made. GYPB not affected.
Produce Anti-Ena
Difficult to transfuse; siblings may be a potential source
What results in the Mk phenotype?
near complete deletion of the GYPA and GYPB genes, therfore MNS null phenotype
Where are P (003) and Globoside (028) antigens found?
- RBCs
- Granulocytes
- Lymphocytes
- Monocytes
Where is the GLOB gene located?
Chromosome 3
What are the antigens of the P system?
- P
- P1
- Pk
- Luke (LKE)
What does the GLOB gene code for and what does it do?
Codes for a transferase that converts Pk antigen into P1 antigen.
What is the most common antigen in the P1PK (003) blood group system?
P1 antigen
How well is the P1 antigen expressed at birth?
How long does it take for the P1 antigen to be expressed?
Poor
May take up to 7 years
Which population has a stronger expression of the P1 antigen?
Black
What might inhibit expression of the P1 antigen, causing some P1 people to type as P1 negative?
Rare dominant gene In(lu) type Lu(a-b-) RBCs
Why may detection of anti-P1 with P1 antigens result in false positives?
Deteriorates rapidly on storage
Where is the P1 and Pk gene located?
What do the genes code for and do?
Chromosome 22
- Transferase which produces P1 (type 2H precursor chains)
- Transferase converts Pk to P
T/F: the Pk antigen is low frequency but is expressed on all RBCs?
True
Why is Pk not readily detected?
P masks
What are the possible P phenotypes?
- P1
- P2
- P
- P1k
- P2k
This antibody is known as the Donath-Landsteiner antibody?
Anti-P
Which antibody is a powerful biphasic hemolysin and what does this mean?
Anti-P
attaches to red cells in the cold and lyses them as they warm back up
Identify the indviduals in which all three P/GlOB system antibodies are found in?
p (anti-P + P1 + Pk)
What are the major diseases associated with the P/GLOB blood group system?
- Hydatid cyst
- Paroxysmal Cold Hemoglobinuria (PCH)
- Tertiary Syphilis
- E.coli associated hemolytic uremic syndrome
How are P antigens affected by enzymes?
Resistant
Describe the relationship between I and i antigens?
Reciprocal relationship; > I =
Newborn red cells have linear stucture with repeating N-acetyllactosamine?
i
The development of ____ depends on th addition of branching N-acetyllactosamine units.
I (big)
Over what period does I(big) develop?
2 years
Identify the rare phenotype in which adults produce alloanti-I?
- retain I-i+
- iadult
When would alloanti-I (anti-I or iso) be an issue?
iadult
should be given i blood (rare)
Anti-I is associated with which diseases/infections?
Cold agglutinin disease and Mycoplasma pneumonia infections
Which antibody commonly interferes with in vitro testing?
Anti-I
- compatibility, antibody studies, and ABO reverse grouping, if done at low temp
- Anti-I can mask prescence of other antibodies
a rare antibody, seen in patients with infectious mononucleosis, myeloid leukemia, alcoholic cirrhosis, and reticulosis?
Anti-i
How do enzymes affect Ii antigens?
Enhanced - ficin and papain
Resistant - DTT, glycine-acid EDTA
What are the two major alleles of the Kell system?
K and k
What are the other alleles of the Kell system?
- Kpa
- Kpb
- Jsa
- Jsb
What is the Kell amorph and its genoype?
What is the result of this phenotype
K0
Homozygous K0K0
Kell null and no Kell antigens produced
What protein is covalently linked to the Kell glycoprotein and essential for Kell antigen expression?
Kx Blood group system
Kx protein
What chromosome is the XK gene located?
X chromosome
T/F - Kell antigens are well developed at birth?
True
What reagents destroy Kell antigens?
Sulfahydryl reagens - DTT or 2-mercaptoethanol (2-ME)
Identify the antigen that is a powerful immunogen, second only to the D antigen?
K antigens
What is the frequency of occurence of the following antigens?
- k
- Kpa (higher in whites)
- Kpb
- Jsa (higher in blacks)
- Jsb
- a = low frequncy
- b = high frequency
- k = high frequency
Define McLeod Syndrome?
What gene is missing?
- Appear to be Kell null but weak expression of k, Kpb and Jsb
- Lack XK gene
How are red cells affected by McLeod syndrome?
- Shortened survival
- acanthocytosis
- increased osmotic fragility
- reticulocytosis
How are K/Kx antigens affected by enzymes?
- Destroyed - trypsin and chymotrypsin when used with thiol reducing agents.
- No effect - ficin and papain
What does the Fy gene produce?
Transmembrane carrier molecule for Duffy Glycoprotein.
What does the Fy gene enable susceptibility to?
invasion by Plasmodium vivax, causative of malaria.
What cells are resistant to malaria?
Fy(a-b-) and lack Fy6 receptor (West Africa, almost all African blacks have this resistance)
What does the Fyx gene produce?
Does not produce a distinct antigen, but inherited weak form of Fyb that reacts with some forms of anti-Fyb
How many Antigens are in the Duffy system? and what are they?
- Fya
- Fyb
- Fy3
- Fy4
- Fy5
- Fy6
What Duffy genes are expressed co-dominatly?
Fya and Fyb
Fya and Fyb are well developed at birth (T/F)?
True
What are Duffy phenotype is found in 68% of American blacks and 100% of African Blacks?
- Fy(a-b-)
What are the different genetic origins of the Fy(a-b-) phenotype?
Why is identifying race important?
Black - also express Fy4 antigen
White - also express Fy3 antigen
Black patient receiving blood from white individuals can make anti-Fy3. this would react strongly with future transfusions of Fy3 positive blood.
How do Proteolytic enzymes affect Duffy antigens?
What does not affect Duffy antigens
- DESTROY
- neuraminidase or purified trypsin
What is the product of the Jk gene?
Urea transport molecule
What is unquie about Jk(a-b-) RBCs?
Resistant to lysis in 2M urea
What are the 3 Jk alleles?
- Jka
- Jkb
- Jk3
What are the two ways in which the Jk(a-b-) phenotype forms?
- Genetic mutation - no Jka, Jkb, or Jk3 produced
- In(Jk) gene - dominant supressor at the Jk locus
- express decreased Jka, Jkb, and Jk3, but too weak to react.
The Jk(a-b-) phenotype has been identified in which populations?
Polynesian
Chinese
Anti-Jka and Anti-Jkb have a notorious blood bank because of these unique characteristics?
Difficult to detect; very weak reactions and antigen dosage effect.
Kidd antibodies are norally made in response to?
Pregnancy or transfusion
Which Antibody is produced by Jk(a-b-) individuals, reacts with all Jka and Jkb positive cells and is insperable from anti-Jka and anti-Jkb?
Anti-Jk3
Why are Kidd antibodies a common cause of Delayed HTRs?
Titre of anti-Jka and anti-Jkb gradually declines in vivo.
The Rare autoantibody-Jka has been documented in (4):
- Warm autoimmune hemolytic anemia
- Methly dopa (aldomet) drug-induced hemolytic anemia
- Recent viral/bacterial infection
- Paraben preserved medications
How does Paraben affect the Jka antigen?
Paraben alters the Jka antigen causes the body to not recognize self and make an autoantibody.
Which blood group is the first example of autosomal linkage in humans?
How many antigens?
- Lutheran
- 19
The LU locus is linked to which locus?
SE Locus
What does the LU gene produce?
What gives rise to the varios Lutheran Antigens?
- Lutheran Glycoprotein
- (antithetical) Amino acid changes gives rise to the various Lutheran Antigens
What are the two most common Lu antigens and their frequency?
Lua - low
Lub - high
What are the three methods that result in the Lu Null Phenotype Lu(a-b-)?
- Dominant In(lu) supressor gene; supresses Lu antigens
- Recessive LuLu gene; inherit 2 null genes
- Recessive X-linked gene; supresses Lu antigens
Of the Lutheran Null Phenotype methods, which results in the formation of Anti-Lua3 which reatcs with all Lua and Lub positive cells?
Recessive LuLu
How do enzymes affect Lu antigens?
Routine BB enzymes like ficin, papain and bromelin have NO effect/ DO NOT destroy Lu antigens.
