Uncommon Blood Groups Flashcards
When was The Lutheran System antibody anti-Lu(a) discovered?
In the serum of a Lupus patient in 1945.
When was The Lutheran System antibody anti-Lu(b) discovered?
In 1956 Lu(b) was described.
How many antigens are in the Lutheran System?
Consists of 20 antigens, 4 of which are antithetical pairs.
What are the four antithetical pairs of the Lutheran System and which pair is low incidence?
- Lu(a) & Lu(b)
- Lu6 & Lu9
- Lu8 & Lu14
- Au(a) & Au(b)—-> low incidence
When are Lutheran antibodies first detectable?
In a ten week old fetus
What tissues are Lutheran antigens not found on?
Lymphocytes, granulocytes, monocytes, or platlets
What as tissues are Lutheran antigens found on?
Blood vessels, brain kidney heart liver, lung, pancreas, placenta.,muscle, skin,etc
When maternal Lutheran ab is absorbed out, what happens?
Likelihood of HDFN increases
How are Lutheran antigens affected by enzymes?
They are destroyed destroyed by trypsin and alpha-chymotrypsin
Which enzymes don’t affect Lutheran antigens?
Ricin and papain
Do Lutheran antibodies react with DTT or AET treated RBCs?
No
Lutheran antibodies are produced by what type of genes?
Allelic codominant genes
How are Lutheran antigens expressed expressed on cord blood cells?
Weakly expressed
Are Lutheran antibodies clinically significant?
Not usually a
Are Lutheran antibodies clinically significant?
Not usually a
Are Lutheran antibodies clinically significant?
Not usually
What isotope are Lutheran antibodies?
IgG
What chromosome contains Gene’s for the Lutheran system?
Chromosome 19
How do the Lutheran antigens hold up in storage?
Fragile when stored
The Lutheran genes have a link to which other gene?
Se gene
What percentage of RBCs express Lu (a)?
5-8%
What percentage of RBCs express Lu (b)?
99%
What are the antibodies of the Lutheran system?
Anti-Lu(a), Anti-Lu(b), and Anti-Lu3
What isotype is anti-Lu(a)?
May be IgG, IgM, or IgA
What isotype is anti-Lu(b)?
Mostly IgG (IgG1), some IgM, IgA
Which Lutheran antibody can be naturally occurring?
Anti-Lu(a)
Will any of the three Lutheran antibodies bind complement?
They rarely bind complement.
Anti-Lu(a) causes what clinical issues?
No immediate HTR, mild delayed HTR
Which Lutheran antibody demonstrates mixed field agglutination reactions?
Anti-Lu(a)
Anti-Lu(b) causes what clinical problems?
Causes mild to moderate HTR; placenta can absorb it out and leads to mild HDFN
What is the most common cause of Anti-Lu(b) in a patient’s serum?
Transfusion or Pregnancy
What is the prevalence of Anti-Lu3?
rare
What enzymes is Anti-Lu3 sensitive to?
DTT, trypsin and chymotrypsin
What Lutheran genotype most commonly produces
Anti-Lu3?
Lu(a-b-)
What isotype is Anti-Lu3?
IgG
What antigens will Anti-Lu3 bind to?
Lu(a) and Lu(b) on red blood cells
Is Anti-Lu3 clinically significant?
No. It is not reported to cause HDFN or HTR.
Blood Group System Definition
one or more antigens produced by alleles at a single locus or loci so closely linked that crossing over does not occur or is very rare.
Alloantibodies can detect
Antigens
Most blood group alleles have this relationship:
Codominant
What are the conventions for writing the names of alleles?
Genes are underlined; allele number is a superscript
What are the conventions for writing the names of antigens?
Antigens are written in regular type with a superscript.
What are the conventions for writing the names of phenotypes?
Described by the antigen present or absent; ex: M+, K-, Jk(a-), Fy(b+)
What are the conventions for writing the names of antibodies?
decribed by placing anti- in front of the antigen; ex: anti-D is the antibody to D antigen.
Who discovered anti-M and anti-N and when?
Landsteiner and Levine in 1927
Who discovered S antigen and when?
Walsh and Montgomery in 1947
little s was discovered in?
1951
U became part of the MNS system in
1953
The highly complex MNS Blood Group System consists of how many antigens?
46 antigens
What are the most common MNS antigens?
M, N, S, s, and U
MNS antigens are found on…
On glycoproteins glycoporin A and/or glycoporin B
M and N antigens attach to…
glycoporin A (GPA)
S and s antigens attach to…
glycoporin B (GPB)
MNS are inherited as the four haplotypes…
MS, Ms, NS, Ns
Which MNS haplotype exhibits linkage disequilibrium?
MS; S is found with M twice as often as with N.
How do M and N antigens react to enzyme treatment of RBCs?
They are destroyed.
M and N antigens are resistant to treatment with what enzymes?
chymotrypsin and DTT
How do S and s antigens react to enzyme treatment of RBCs?
Destruction can be variable
How S and s antigens are react to treatment with enzymes?
They are destroyed by chymotrypsin, but resist treatment with DTT.
Which MNS genotype is often deficient in GPB?
S-s- U-
Which MNS antigen is high prevalence?
U
U- RBCS are almost always…
S-s-
S-s- genotype often goes with what antigen?
U+
How does U antigen react to enzyme treatment?
It is generally resistant to enzyme treatment.
What isotype is anti-M?
IgM and/or IgG
Does anti-M show dosage?
yes
How common is anti-M and how is it stimulated?
It is common and naturally occurring.
What special environmental condition do some anti-M prefer?
Some react best in an acid environment; pH 6.5
Is anti-M clinically significant?
Not always. It is rarely implicated in both acute and delayed HTR, but it may cause rare and severe HDFN.
Anti-N prevalence?
Rare
How does anti-N react?
It reacts at room temperature and below.
Is anti-N clinically significant?
No. It is rarely implicated in acute and delayed transfusion reaction.
Does ant-N show dosage?
Yes.
Autoanti-N has been reported to cause….
a few cases of AIHA
Anti-N occurred in a group of dialysis patients after…
the dialysis machine was cleaned with formaldehyde.
Anti-S and anti-s are what isotype?
IgG
Anti-S and anti-s react when?
at 37 degrees and at AHG
Do anti-S and anti-s show dosage?
They may.
Are anti-S and anti-s clinically significant?
Yes. They have been implicated in HTR and have caused severe and fatal HDFN.
Autoanti-S has been implicated in…
AIHA
Anti-U is what isotype?
IgG
Anti-U is most commonly produced in what phenotypes individuals?
S-s-
Autoanti has been reported in a case(s) of…
AIHA
Is anti-U clinically significant?
It has been reported in mild to severe HTR and HDFN.
And delayed transfusion reactions.
What diseases are associated with the MNS system?
E. coli infection and malaria
How does the MNS system interact with E. coli?
GPA acts as a receptor for certain strains of E.coli.
How does the MNS system interact with Plasmodium falciparum?
GPA and GPB act as receptor sites for the malarial parasite.
Who discovered the Kell System and when?
Coombs discovered just after the development of AHG in 1946.
How many antigens are associated with the Kell System?
36
What are most important Kell antigens?
K, k, Kp(a), Kp(b), Js(a), Js(b)
Where are Kell antigens found?
mostly on RBCs, but also on bone marrow, fetal liver, testes, brain, lymphoid, heart, skeletal muscle
During what part of the life cycle are kell antigens present?
They are well-developed at birth.
How do Kell antigens react to enzyme treatment?
They are not denatured by routine blood bank enzymes.
What combination of reducing agent and enzymes will it take to denature a Kell antigen?
They are sensitive to a mix of trypsin, alpha chymotrypsin, and reducing agents(DTT, EZAP, EEGA).
What genes are responsible for normal Kell antigen production?
KEL and Xk
What does KEL encode for?
Kell glycoprotein
What does Xk encode for?
—–protein
The FDA requires that K and k antigens . . .
must be included on all antigen profiles.
What is the prevalence of K or KEL 1 antigens?
Prevalent in about 9% of people of European origin and 1.5% in people of African origin and rare in people of East Asian origin.
What is the prevalence of k or KEL 2 antigens?
High incidence in all populations
What is the prevalence of Kp(a) or KEL 3 antigens?
Low incidence; <2% European only
What is the prevalence of Kp(b) or KEL 4 antigens?
High incidence in all populations, >99%
What is the prevalence of Js(a) or KEL 6 antigens?
20% among those of African origin.
What is the prevalence of Js(b) or KEL 7 antigens?
High incidence in all populations
How do Kell antigens rate in clinical significance among the other blood groups?
Excluding ABO, Kell is second only to D antigen in creating antibodies; Kell antigens are strongly immunogenic.
How many antigens are in the Kell System?
36 antigens
What are the three allelic pairs of the Kell system?
K and k
Kp(a) and Kp(b)
Js(a) and Js(b)
What isotype are Kell antibodies?
IgG
How are Kell antibodies stimulated?
by pregnancy or transfusion
Are Kell antibodies clinically significant and why?
Yes. Can cause severe HDFN and HTR. It suppresses erythropoiesis in a newborn in addition to causing hemolysis.
Can patients with anti-K have K+ blood for transfusion?
No. They always need K- blood.
What is the most common antibody seen in the blood bank, outside of ABO and Rh?
Anti-K
When are Kell antibodies detected?
at AHG of the antibody screen
What isotype is anti-K?
IgG, specifically IgG1
What stimulates anti-K?
Pregnancy or transfusion
What isotype is anti-k?
IgG, specifically IgG1
When is anti-k detected?
Most often at AHG
What is the prevalence of anti-Kp(a), Js(a)?
Rare because few people are exposed to these antigens (only by pregnancy and transfusion)
How are anti-Kp(a), Js(a) detected most commonly?
Detected through unexpected incompatible crossmatches or HDFN
What other Kell antibody is similar to anti-Kp(a), anti-Js(a), Anti-Kp(b), and Anti-Js(b)serologically?
Anti-K
What is the prevalence of Anti-Kp(b) and Anti-Js(b)?
Rare because few people are exposed to these antigens.
Is anti-k clinically significant?
Yes. It can cause HTR and HDFN. And Intravascular hemolysis.
K(null) phenotype is expressed as
no Kell antigens are expressed; antigens may somehow be involved in membrane integrity
K (mod) phenotype is expressed as
very weak expression of Kell antigens
K(x) phenotype is expressed as
a part of its own blood group system, but is linked to the Kell glycoprotein by a single disulfide bond
What is the McLeod phenotype?
It occurs because of the absence of K(x) antigen and reduced expression of Kell; It is rare and leads to decreased RBC survival.
What is McLeod syndrome?
It is an X-linked genotype of absent K(x) and reduced Kell expression.
What are the diseases associated with McLeod syndrome?
Acanthocytosis
Neuromuscular disease
Psychiatric involvement
Chronic Granulomatous Disease
Are transfusions a good treatment for a pt with McLeod Syndrome?
No. Transfusions should be avoided.
What are characteristics of Kell autoantibodies?
Most are directed against high prevalence antigens.
Mimicking specificities have been reported
Where did The Duffy System get its name?
It was named for Mr. Duffy, a multiple transfused hemophiliac, with anti-Fy(a); Anti-Fy(b) was discovered a year later.
What year was Fy(a-b-) phenotype described?
1955
Fy (a-b-) phenotype resists what infections?
P. knowlesi and P. vivax
How many Duffy antigens?
5 antigens
What is the biochemical structure of the Duffy antigens?
antigens reside on a glycoprotein known as the Duffy antigen receptor for chemokines or DARC
People of African ancestry produce a third Duffy allele, Fy, that…
Has no glycoprotein on their RBCs
What are the two antigen common among European and Asian populations?
Fy(a) and Fy(b)
Fy=
Duffy
What are the four Duffy phenotypes?
Fy(a+b-)
Fy(a+b+)
Fy(a-b+)
Fy(a-b-)
How do antigens Fy(a) and Fy(b) hold up in storage?
may deteriorate
How do antigens Fy(a) and Fy(b) react to enzymes?
destroyed by proteolytic enzymes and by ZZAP
When are Fy(a) and Fy(b) antigens begin to be expressed?
well developed at birth, found in umbilical cord RBCs
Where are antigens Fy(a) and Fy(b) found?
endothelial cells, brain, lung alveoli, renal epithelium
What isotype are Anti-Fy(a) and Anti-Fy(b)?
Mostly IgG, specifically IgG1
Do an Anti-Fy(a) and Anti-Fy(b) show dosage?
Yes
How do Anti-Fy(a) and Anti-Fy(b) react to enzymes?
destroyed by enzymes
What is the prevalence of Anti-Fy(a) and Anti-Fy(b)?
anti-Fy(a) is 20x more common than anti-Fy(b)
Are Anti-Fy(a) and Anti-Fy(b) clinically significant?
Yes. Both can cause HTR and HDFN–acute and delayed
How do Anti-Fy(a) and Anti-Fy(b react best?
at AHG phase
Are there Anti-Fy(a) and Anti-Fy(b) autoantibodies?
yes. rare autoantibodies have been reported
Fy3 antigen prevalence
present in about 100% whites, 32% of blacks
What is Fy3 antigen’s reaction to enzymes?
not destroyed by proteolytic enzymes
What antigens must be present for Fy3 to be expressed?
Fy(a) and Fy(b)
When is Fy3 antigen first expressed?
Expressed on cord RBCS, and expression increases after birth.
What is the isotype of anti-Fy3 antibody and does it bind complement?
IgG, rarely binds complement
When does anti-Fy3 antibody react best?
detected at AHG
What is the prevalence of anti-Fy3?
rare
What is the prevalence of Fy5 antigen?
32% in black pop, 99.9% in everybody else
only present when either Fy(a) or Fy(b) is present and also requires a normal Rh (not Rh null)
How does Fy5 antigen react to enzymes?
resists treatment with ficin and papain, and DTT
What isotype is anti-Fy5?
IgG
How does anti-Fy5 react to enzymes?
reacts best at AHG phase
Is anti-Fy5 clinically significant?
can cause mild transfusion reactions; HDFN is unknown
How are Duffy antibodies summarized?
by pregnancy and transfusion
Do Duffy antibodies bind complement?
No
Do Duffy antibodies show dosage?
Yes
Are Duffy antibodies clinically significant?
Yes. Cause HTR, but do not commonly cause HDFN.
Patients with the antibody should receive antigen negative RBCs for transfusion and AHG crossmatch.
The genotype Fy(a-b-) confers resistance to what disease?
Malaria, it confers a selective advantage.
Explain how the Duffy glycoprotein interacts with the malarial parasite.
It is a receptor for Plasmodium vivax.
The Duffy blood group is a possible receptor for…
chemokines. It removes excess, cleans up excess.
Who discovered The Kidd System and when?
Discovered in 1951 in Mrs. Kidd whose infant suffered from HDFN.
What are The Kidd System Antigens?
Jk(a), Jk(b), Jk3
What is the composition of the Kidd antigens?
glycoprotein
Which Kid antigens are products of antithetical alleles?
Jk(a) and Jk(b)
What is the prevalence of the Kidd antigens?
Jk(a) and Jk(b) are common in most people. Jk(a) is more common than Jk(b) in people of African descent.
When are the Kidd antigens detectable?
Detected at 7-11 weeks gestation. They are well-developed at birth.
Are The Kidd antigens clinically significant?
No. Cause rare HDFN. Not very immunogenic.
How do Kidd antigens react to enzymes?
Not denatured by enzymes.
What function are Kidd antigens thought to have for RBCs?
Urea transporter in RBCs, across membrane as RBCs pass though the kidneys.
Where are Kidd antigens found?
RBCs. Not on plts, monocytes, granulocytes, or lymphocytes
What is the prevalence of anti-Jk(a) and anti-Jk(b)?
Not common.
What are the Kidd antibodies?
anti-Jk(a) and anti-Jk(b)
When do anti-Jk(a) and anti-Jk(b) react?
AHG
Do anti-Jk(a) and anti-Jk(b) demonstrate dosage?
Yes
Are anti-Jk(a) and anti-Jk(b) clinically significant?
Can cause severe, acute HTR.
**Common cause of delayed HTR
Very rarely cause HDFN
Have been implicated in acute renal transplant rejection.
Do anti-Jk(a) and anti-Jk(b) bind complement?
Approximately 50% antibody binds complement.
titers drop quickly and can go undetected, thus previous records are useful.
Amanestic response.
