Transcript Other Blood Groups

Other Blood Groups
The Kell Blood Group System
Background information
The Kell blood group system was discovered
in 1946.
 Number of Kell antigens: > 20
 These antigens are the third most potent, after
those of the ABO and Rh blood groups, at
triggering an immune reaction.
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Molecular information
The KEL gene is found on chromosome 7
 The KEL gene is highly polymorphic, with
different alleles at this locus encoding the
25 antigens that define the Kell blood
group.
 The Kell protein is a polypeptide chain of
732 amino acids in length that becomes
glycosylated at five different sites. It makes
a single pass through the RBC membrane.
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Kell Blood Group System
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XK gene produces Kx substance, which is a precursor of
of Kell Ags
Kel genes convert Kx substance into the Kell Ags on
RBCs
K (Kell) & k (cellano) are produced by allelic genes, this
results into 3 phenotypes:
 K+k- (genotype KK)
 K+k+ (genotype Kk)
 K-k+ (genotype kk)
Other allelic genes include: Kpa/Kpb, Jsa/Jsb
XK Gene (Chromosome X)
KEL Gene
RBC
Kx
Kell system glycoprotein: Kell Ag’s reside
here.
Frequency of Kell phenotypes
Phenotype
Caucasians
Blacks
K-k+
91 %
98 %
K+k-
0.2 %
Rare
K+k+
8.8
2
Kx Substance
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Kx substance is present on RBCs & WBCs
Kell genes convert Kx substance into the Kell Ags
on RBCs
Kell genes do not convert Kx on WBCs
McLeod Phenotype
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Absence of Kx proteins
in RBCs membrane lead
to McLeod Phenotype
This absence cause:
 abnormal RBCs shape
(acanthocytes) &
reduced in-vivo
survival.
Chronic Granulomatous Disease
Absence of Kx proteins in WBCs cause
CGD
 Leukocytes are able to phagocytose but not
to kill bacteria
 Patients with CGD have recurrent bacterial
infections
 Patients who lack Kx on RBCs & WBCs
have both Mcleod and CGD
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Kell Null (K0) Phenotype
Kx
1. K0 is a silent Kell allele
2. When homozygous
K0K0 inherited no Kell
system antigens are
expressed.
3. Kx antigen expression
is enhanced
4. Very rare
Kell Antibodies
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K- individuals produce anti-K when exposed to
K+ cells
– Frequency of K is low (9%), easy to find
compatible blood for the patient with anti-k.
On the other hand frequency of k antigen is
99.9%
– Difficult to find blood
Antibodies produced against Kell antigens
Kell Abs
Clinically Significant
Abs class
Yes
IgG , (rarely) IgM
Thermal range
HDNB
4 - 37
Yes
Transfusion Reactions
Extravascular
Intravascular
Yes
Rare
Duffy Blood Group System
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The Duffy blood group was discovered in 1950.
The Duffy glycoprotein is encoded by the FY gene, found
on chromosome 1 , of which there are two main alleles,
FYA and FYB. They are codominant.
The Duffy gene codes for a glycoprotein also found in
other tissues: brain, kidney, spleen, heart and lung.
The Duffy glycoprotein is a transmembrane protein
Five alleles at Duffy locus, the most important: Fya, Fyb &
Fy (Silent Allele)
Fya is more immunogenic than Fyb
Different genes
Fy(a-b-) blacks do not produce anti-Fya or
anti-Fyb following transfusion with Fy(a+)
or Fy(b+) blood
 Fy(a-b-) Caucasians become sensitized
following transfusion with Fy(a+) or
Fy(b+) blood
 This suggest that Fy(a-b-) phenotype arises
from different genes in the two populations
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Duffy Antigens
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Fya, Fyb antigens are Destroyed by enzymes
Abs DO NOT agglutinate enzyme treated cells
Moderately immunogenic.
Duffy Antigens
Phenotype
Caucasians %
Blacks %
Fy (a+b+)
49
2
Fy (a+b-)
18
14
Fy (a-b+)
33
19
Fy (a-b-)
rare
65
Duffy Antibodies
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IgG antibodies and can
activate complement
Anti- Fya is more
frequently encountered
Anti- Fyb is more
frequently found in
patients produced
multiple alloantibodies
Duffy Abs
Clinically
Significant
Abs class
Yes
IgG
Thermal range
HDNB
4 - 37
Yes
Transfusion Reactions
Extravascular
Intravascular
Yes
Yes
Duffy and Malaria
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Black people with the Duffy phenotype of Fy(a–b–)
appear to have resistance to Plasmodium vivax &
Plasmodium knowlesi causative agents of Malaria.
– Duffy antigens appear to be a receptor for the P. vivax
organism and when the antigen is not present on the
red blood cell membrane P. vivax is unable to access
the red blood cell
– Some area’s of West Africa are 100% Fy(a–b–).
Plasmodium falciparum binds to RBCs at integral
glycophorin A & B
Kidd Blood Group System
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The Kidd blood group was discovered in 1950.
The Kidd gene is located on chromosome 18
Three alleles: Jka, Jkb, Jk
– Codominant Inheritance
– Jk is a silent allele (amorph)
The Kidd protein is an integral protein of the RBC
membrane.
Kidd Phenotype Frequencies
Phenotype
Caucasians (%)
Jk (a+ b-)
29
Jk (a+ b+)
49
Jk (a- b+)
22
Jk (a- b-)
Exceedingly rare
Kidd Antigens & Antibodies
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Ags are well developed at birth
Have tendency to drop to low or undetectable levels
following formation.
Abs are of IgG type & can activate complement (Anti-Jka,
Anti-Jkb )
Produced following transfusion or pregnancy
Can cause HDNB
They are also a very common cause of delayed HTRs
Ii Blood Group
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Found nearly on all RBCS
Their products are transferase enzymes that attach
repeating units of Gal and GlcNAc to the ABO
Precursor Substance.
Big I gene codes for branching of the Precursor
Substance.
Ii Antigens
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Little i antigen is LINEAR
– Found on cord cells, predominantly
Big I antigen is BRANCHED
– Gradually convert from i to I during the first 18 months of life. Not
all i converted to I, some i still present on adult cells, normally.
Rare adult individuals termed iadult do not express i Ag on their red cells
The I and i antigen sites are considered uncompleted ABH active
chains.
When ABH are removed from RBCs more I Ags are expressed
–
I structure located beneath the ABH Ags
I Antibodies: Anti-I
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Anti-I is naturally occurring
often due to a Mycoplasma
pneumoniae infection
Anti-I reacts with all adult cells
(including patient’s own, all
reagent cells, all donor cells)
Anti-I does not react with cord
cells
Auto-anti-I is a common “cold
agglutinin”
Anti-I Abs
Clinically
Significant
Abs class
Rare
IgM
Thermal range
HDNB
4 - 10
No
Transfusion Reactions
Extravascular
Intravascular
No
rare
Antii Antibodies
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Antii is rarely found in healthy individuals
Reacts preferably with cord cells
anti-i can be found secondary to Infectious
Mononucleosis.
– Transient: Only present with active disease
MNSs Blood Group System
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The antigens M and N are produced by codominant alleles
closely linked to the S and s genes, which are also
co-dominant.
Chromosome 4 contains these linked genes
Genes produce two distinct glycophorins or
sialyglycoproteins (SGP) on the RBC membrane.
MN Genetics
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MN Locus genes produce Glycophorin A (GPA)
– M-GPA’s 1st five aa’s = Serine-Ser-Thr-ThrGlycine
– N-GPA’s 1st five aa’s = Leucine-Ser-Thr-ThrGlutamic acid
– Amino acids (aa) 2, 3 & 4 are the same for
both
Glycophorin A (GPA) is a glycoprotein also
known as MN-sialoglycoprotein
MN Genotypes & Phenotypes
Phenotype
Genotype
Frequency %
M+N-
MM
30
M+N+
MN
50
M-N+
NN
20
Ss Genetics
Ss genes code for the production of
Glycophorin B(GPB)
 S glycophorin B has Methionine aa at
position 29
 s glycophorin B has Threonine aa at
position 29
 Glycophorin B (GPB) is a glycoprotein also
known as Ss-sialoglyprotein
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Ss Genotypes & Phenotypes
Phenotype
Genotype
S+s-
Frequency %
Caucasians
Blacks
SS
11
6
S+s+
Ss
44
24
S-s+
ss
45
68
S-s-
S u su
0
2
•
U antigen is a high incident antigen NOT seen in individuals who lack
both S and s antigens.
•
Individuals who lack this antigen (<1%) have a high likelihood of forming
anti-U as well as anti-S and anti-s.
Anti-M Antibodies
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Variability of
reactivity (Dosage)
 Strong reactions
with RBCs
homozygous for
MM
 Weak reactions
with RBCs
heterozygous MN
Anti-M Abs
Clinically
Significant
Abs class
Seldom
IgG & IgM
Thermal range
HDNB
4 – 22
Rare 22-37
rare
Transfusion Reactions
Extravascular
Intravascular
Rare
No
Anti-N antibodies
• Naturally occurring cold
agglutinin
• Can form in patients with
renal Failure
• During dialysis with
formaldehyde sterilized
equipment
• Formaldehyde may alter the
N Ag structure making it
appear foreign
Anti-N Abs
Clinically
Significant
Abs class
IgM
No
Thermal range
HDNB
4 - 22
No
Transfusion Reactions
Extravascular
Intravascular
No
No
Anti-S and Anti-s antibodies
Anti-S Abs
Clinically
Significant
Abs class
IgG & IgM
Sometimes
Anti-s Abs
Clinically
Significant
Abs class
IgG
Yes
Thermal range
HDNB
Thermal range
HDNB
4 - 37
Yes
4 - 37
Yes
Transfusion Reactions
Transfusion Reactions
Extravascular
Intravascular
Extravascular
Intravascular
Yes
No
Yes
No
P Blood Group System
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Genetics: These genes code for enzymes that
sequentially add sugars to precursor substance.
This system is related to the ABO, Le and Ii systems.
Genes: P1, Pk, P and lower case p (silent allele)
All antigens are expressed on glycolipids on red cells
Phenotypes, Detectable Antigens & Frequencies
Phenotype
Detectable
Antigens
Frequencies
P1
P1, P
79%
P2
P
21%
Pk1
P, Pk
Rare
Pk2
Pk
Rare
p
N/A
Rare
•Pk is the precursor of P.
•Rare individuals do not convert Pk into P.
•Those will have Pk on RBCs.
Whites %
Anti-P1 Antibodies
Naturally occcurring
Abs found in the serum
of P2 Individuals
Anti-P1 Abs
Clinically
Significant
Abs class
IgM
occasionally
Thermal range
HDNB
4 – 22
Yes
Rare 22-37
Transfusion Reactions
Extravascular
Intravascular
No
Rare
Allo Anti-P Antibodies
Naturally occcurring
Abs found in the serum
of Pk and p Individuals
Allo Anti-P Abs
Clinically
Significant
Abs class
Yes
Rare IgG
Thermal range
HDNB
4 – 37S
Rare
IgM
Transfusion Reactions
Extravascular
Intravascular
No
Yes
Auto anti-P Antibodies
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It is an IgG biphasic Ab
associated with
Paroxysmal Cold
Hemoglobinuria (PCH)
Binds complement at
cold temperatures and
activates that
complement in warm
temperatures lysing the
red blood cells.
Auto Anti-P Abs
Clinically
Significant
Abs class
IgG
Yes
Biphasic
HDNB
Binds at 0
Rare
Hemolysis 37
Transfusion Reactions
Extravascular
Intravascular
Rare
Yes
Anti Tja Antibodies
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Combination of anti-P, anti-P1 & anti-Pk
Found in serum of individuals who have no P, P1 &
Pk Ags on red cells