Other Blood Groups 1 Mazen

1

Other Blood Groups

Kell, Duffy, Kidd, Ii, MNSs & P

2M. Zaharna Blood Bank 2009

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.


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.



Kell 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 phenotypes

Phenotype Caucasians Blacks

K-k+ 91 % 98 %

K+k- 0.2 % Rare

K+k+ 8.8 2


Kx 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 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 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 Antibodies K- individuals produce anti-K when

exposed to K+ cells Frequency of K+ is low (9%), easy to find blood

On the other hand frequency of k is 99.9% k- individuals produce anti-k when exposed to

k+ cells Difficult to find blood


Antibodies produced against Kell antigens

Kell AbsClinically

Significant

Yes

Abs class

IgG (rarely) IgM

Thermal range

4 - 37

HDNB

Yes

Transfusion Reactions

Extravascular Intravascular

Yes Rare


Duffy Blood Group System


Duffy 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



Duffy Antigens

Phenotype Frequencies

Phenotype Caucasians % Blacks

%

Fy (a+b+) 49 2

Fy (a+b-) 18 14

Fy (a-b+) 33 19

Fy (a-b-) rare 65


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


Duffy Antigens Fya, Fyb antigens are Destroyed by enzymes

Abs DO NOT agglutinate enzyme treated cells

Moderately immunogenic Fya is more immunogenic than Fyb


Duffy 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 AbsClinically

Significant

Yes

Abs class

IgG

Thermal range

4 - 37

HDNB

Yes



Yes Yes


Duffy 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 System


Kidd 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 Frequencies

Phenotype Caucasians (%)

Jk (a+ b-) 29

Jk (a+ b+) 49

Jk (a- b+) 22

Jk (a- b-) Exceedingly rare


Phenotype Frequencies

What is the purpose of learning the phenotype frequencies of each blood group antigen?

– When crossmatches are required it helps the Tech know how many units to crossmatch or antigen type to find compatible blood.

If a patient has anti-Jka antibody how many RBC units need to be antigen typed to find 2 compatible units?

78% of the population is positive for the antigen therefore 22% are NEGATIVE for the antigen. Approximately 2 out of 10 units are compatible. Need to antigen type 10 units.


Kidd 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 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 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-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



No rare


Antii 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 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 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 & Phenotypes

Phenotype Genotype Frequency %

M+N- MM 30

M+N+ MN 50

M-N+ NN 20


MNSs Antigens

RBC

Glycophorin A

Glycophorin B

M

N

SsU

M & N only differ in their amino acid

sequence at positions 1 and 5

S & s only differ in their amino acid

sequence at position 29

….5, 4, 3, 2, 1 (NH2 end)COOH end …..


Ss Genetics

Ss genes code for the production of Glycophorin B(GPB)

S glycophorin B has Methionine at aa position 29

s glycophorin B has Threonine at aa position 29

Glycophorin B (GPB) is a glycoprotein also known as Ss-sialoglyprotein


Ss Genotypes & Phenotypes

Phenotype GenotypeFrequency %

Caucasians Blacks

S+s- SS 11 6

S+s+ Ss 44 24

S-s+ ss 45 68

S-s- Susu 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.


Rare Alleles Rare low incidence alleles found on MN

locus

Some may result from crossing over of genes of glycophorin A & B

Such crossing over results in hybrid sialoglycoproteins


Anti-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



Rare No


Anti-N antibodiesAnti-N Abs

Clinically Significant

No

Abs class

IgM

Thermal range

4 - 22

HDNB

No



No No

• 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 Abs


Sometimes

Abs class

IgG & IgM

Thermal range

4 - 37

HDNB

Yes


Extravascular

Intravascular

Yes No

Anti-s AbsClinically

Significant

Yes

Abs class

IgG

Thermal range

4 - 37

HDNB

Yes


Extravascular

Intravascular

Yes No


P 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 %

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.

Phenotypes, Detectable Antigens & Frequencies


Anti-P1 Antibodies

Anti-P1 Abs


occasionally

Abs class

IgM

Thermal range

4 – 22

Rare 22-37

HDNB

Yes



No Rare

Naturally occcurring Abs found in the serum of P

2

Individuals


Allo Anti-P Antibodies

Allo Anti-P AbsClinically

Significant

Yes

Abs class

IgM

Rare IgG

Thermal range

4 – 37S

HDNB

Rare



No Yes

Naturally occcurring Abs found in the serum of Pk and p

Individuals


Auto anti-P Antibodies 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



Rare Yes


Anti Tja Antibodies

Combination of anti-P, anti-P1 & anti-Pk

Found in serum of individuals who have no P, P1 & Pk Ags on red cells

Documents

Other Blood Groups 1 Mazen