Other Blood Groups. The Kell Blood Group System Background information The Kell blood group system was discovered in 1946. Number of Kell antigens: >
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Other Blood GroupsOther Blood Groups
The Kell Blood Group SystemThe Kell Blood Group System
Background informationBackground information
The Kell blood group system was discovered in 1946.
Number of Kell antigens: > 20These antigens are the third most potent, after
those of the ABO and Rh blood groups, at triggering an immune reaction.
Molecular informationMolecular information
The KEL gene is found on chromosome 7The 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.
Kell Blood Group SystemKell Blood Group System
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
Kx
XK Gene (Chromosome X)
Kell system glycoprotein: Kell Ag’s reside here.
KEL Gene
RBC
Frequency of Kell phenotypesFrequency of Kell phenotypes
PhenotypeCaucasiansBlacks
K-k+91 %98 %
K+k-0.2 %Rare
K+k+8.82
Kx SubstanceKx Substance
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 PhenotypeMcLeod Phenotype
Absence of Kx proteins in RBCs membrane lead to McLeod Phenotype
This absence cause: abnormal RBCs shape
(acanthocytes) & reduced in-vivo survival.
Chronic Granulomatous DiseaseChronic 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
Kell Null (K0) PhenotypeKell Null (K0) Phenotype
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
Kx
Kell AntibodiesKell Antibodies
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 antigensAntibodies produced against Kell antigens
Kell AbsClinically Significant
Yes
Abs class
IgG , (rarely) IgM
Thermal range
4 - 37
HDNB
Yes
Transfusion Reactions
ExtravascularIntravascular
YesRare
Duffy Blood Group SystemDuffy Blood Group System
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 genesDifferent 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
Duffy AntigensDuffy Antigens
Fya, Fyb antigens are Destroyed by enzymes Abs DO NOT agglutinate enzyme treated cells Moderately immunogenic.
Duffy AntigensDuffy Antigens
PhenotypeCaucasians % Blacks %
Fy (a+b+)492
Fy (a+b-)1814
Fy (a-b+)3319
Fy (a-b-)rare65
Duffy AntibodiesDuffy Antibodies
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
Yes
Abs class
IgG
Thermal range
4 - 37
HDNB
Yes
Transfusion Reactions
ExtravascularIntravascular
YesYes
Duffy and MalariaDuffy and Malaria
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 SystemKidd Blood Group System
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 FrequenciesKidd Phenotype Frequencies
PhenotypeCaucasians (%)
Jk (a+ b-)29
Jk (a+ b+)49
Jk (a- b+)22
Jk (a- b-)Exceedingly rare
Kidd Antigens & AntibodiesKidd Antigens & Antibodies
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 GroupIi Blood Group
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 AntigensIi Antigens
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-II Antibodies: Anti-I
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 AbsClinically Significant
Rare
Abs class
IgM
Thermal range
4 - 10
HDNB
No
Transfusion Reactions
ExtravascularIntravascular
Norare
AntiAntii Antibodiesi Antibodies
Antii 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 SystemMNSs Blood Group System
The antigens M and N are produced by co-dominant 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 GeneticsMN Genetics
MN Locus genes produce Glycophorin A (GPA)– M-GPA’s 1st five aa’s = Serine-Ser-Thr-Thr-
Glycine– N-GPA’s 1st five aa’s = Leucine-Ser-Thr-Thr-
Glutamic 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 & PhenotypesMN Genotypes & Phenotypes
PhenotypeGenotypeFrequency %
M+N-MM30
M+N+MN50
M-N+NN20
Ss GeneticsSs 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
Ss Genotypes & PhenotypesSs Genotypes & Phenotypes
PhenotypeGenotypeFrequency %
CaucasiansBlacks
S+s-SS116
S+s+Ss4424
S-s+ss4568
S-s-Susu02
• 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 AntibodiesAnti-M Antibodies
Variability of reactivity (Dosage) Strong reactions
with RBCs homozygous for MM
Weak reactions with RBCs heterozygous MN
Anti-M AbsClinically Significant
Seldom
Abs class
IgG & IgM
Thermal range
4 – 22
Rare 22-37
HDNB
rare
Transfusion Reactions
ExtravascularIntravascular
RareNo
Anti-N antibodiesAnti-N antibodies
Anti-N Abs
Clinically Significant
No
Abs class
IgM
Thermal range
4 - 22
HDNB
No
Transfusion Reactions
ExtravascularIntravascular
NoNo
• 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-S and Anti-s antibodiesAnti-S and Anti-s antibodies
Anti-S AbsClinically
Significant
Sometimes
Abs class
IgG & IgM
Thermal range
4 - 37
HDNB
Yes
Transfusion Reactions
ExtravascularIntravascular
YesNo
Anti-s AbsClinically
Significant
Yes
Abs class
IgG
Thermal range
4 - 37
HDNB
Yes
Transfusion Reactions
ExtravascularIntravascular
YesNo
P Blood Group SystemP Blood Group System
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
PhenotypeDetectable Antigens
Frequencies
Whites %
P1P1, P79%
P2P21%
Pk1P, PkRare
Pk2PkRare
pN/ARare•Pk is the precursor of P.
•Rare individuals do not convert Pk into P.
•Those will have Pk on RBCs.
Phenotypes, Detectable Antigens & FrequenciesPhenotypes, Detectable Antigens & Frequencies
Anti-PAnti-P1 1 AntibodiesAntibodies
Anti-P1 Abs
Clinically Significant
occasionally
Abs class
IgM
Thermal range
4 – 22
Rare 22-37
HDNB
Yes
Transfusion Reactions
ExtravascularIntravascular
NoRare
Naturally occcurring Abs found in the serum of P
2 Individuals
Allo Anti-PAllo Anti-P AntibodiesAntibodies
Allo Anti-P AbsClinically
Significant
Yes
Abs class
IgM
Rare IgG
Thermal range
4 – 37S
HDNB
Rare
Transfusion Reactions
ExtravascularIntravascular
NoYes
Naturally occcurring Abs found in the serum of Pk and p
Individuals
Auto anti-PAuto anti-P AntibodiesAntibodies
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 AbsClinically
Significant
Yes
Abs class
IgG
Biphasic
Binds at 0
Hemolysis 37
HDNB
Rare
Transfusion Reactions
ExtravascularIntravascular
RareYes
Anti TjAnti Tja a AntibodiesAntibodies
Combination of anti-P, anti-P1 & anti-Pk
Found in serum of individuals who have no P, P1 & Pk Ags on red cells
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