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