1. Other Blood Groups

2. The Kell Blood Group System

3. 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.

4. 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.

5. 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

6. XK Gene (Chromosome X) KEL Gene RBC Kx
Kell system glycoprotein: Kell Ag’s reside here.
KEL Gene
RBC

7. Frequency of Kell phenotypes
Caucasians
Blacks
K-k+
91 %
98 %
K+k-
0.2 %
Rare
K+k+
8.8 2

8. 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

9. McLeod Phenotype
Absence of Kx proteins in RBCs membrane lead to McLeod Phenotype
This absence cause:
abnormal RBCs shape (acanthocytes) & reduced in-vivo survival.

10. 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

11. Kell 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

12. Kell 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

13. Antibodies produced against Kell antigens
Kell Abs
Clinically Significant
Yes
Abs class
IgG , (rarely) IgM
Thermal range
4 - 37
HDNB
Transfusion Reactions
Extravascular
Intravascular
Rare

14. 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

15. 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

16. Duffy Antigens Fya, Fyb antigens are Destroyed by enzymes
Abs DO NOT agglutinate enzyme treated cells
Moderately immunogenic.

17. Duffy Antigens 65 49 18 Phenotype Caucasians % Blacks % Fy (a+b+) 214
Fy (a-b+) 33 19
Fy (a-b-)
rare 65

18. Clinically Significant Transfusion Reactions
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 Abs
Clinically Significant
Yes
Abs class
IgG
Thermal range
4 - 37
HDNB
Transfusion Reactions
Extravascular
Intravascular

19. 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

20. 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.

21. Kidd Phenotype Frequencies
Caucasians (%)
Jk (a+ b-) 29
Jk (a+ b+) 49
Jk (a- b+) 22
Jk (a- b-)
Exceedingly rare

22. 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

23. 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.

24. 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

25. Clinically Significant Transfusion Reactions
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 Abs
Clinically Significant
Rare
Abs class
IgM
Thermal range
4 - 10
HDNB No
Transfusion Reactions
Extravascular
Intravascular
rare

26. Antii Antibodies 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

27. 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.

28. 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

29. MN Genotypes & Phenotypes
Frequency %
M+N- MM 30
M+N+ MN 50
M-N+ NN 20

30. 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

31. Ss Genotypes & Phenotypes
Frequency %
Caucasians
Blacks
S+s- SS 11 6
S+s+ Ss 44 24
S-s+ ss 45 68
S-s-
Susu 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. 

32. Clinically Significant Transfusion Reactions
Anti-M Antibodies
Anti-M Abs
Clinically Significant
Seldom
Abs class
IgG & IgM
Thermal range
4 – 22
Rare 22-37
HDNB
rare
Transfusion Reactions
Extravascular
Intravascular
Rare No
Variability of reactivity (Dosage)
Strong reactions with RBCs homozygous for MM
Weak reactions with RBCs heterozygous MN

33. Clinically Significant Transfusion Reactions
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 No
Abs class
IgM
Thermal range
4 - 22
HDNB
Transfusion Reactions
Extravascular
Intravascular

34. Anti-S and Anti-s antibodies
Anti-S Abs
Clinically Significant
Sometimes
Abs class
IgG & IgM
Thermal range
4 - 37
HDNB
Yes
Transfusion Reactions
Extravascular
Intravascular No
Anti-s Abs
Clinically Significant
Yes
Abs class
IgG
Thermal range
4 - 37
HDNB
Transfusion Reactions
Extravascular
Intravascular No

35. 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

36. Phenotypes, Detectable Antigens & Frequencies
Whites % P1
P1, P
79% P2 P
21%
Pk1
P, Pk
Rare
Pk2 Pk p
N/A
Pk is the precursor of P.
Rare individuals do not convert Pk into P.
Those will have Pk on RBCs.

37. Clinically Significant Transfusion Reactions
Anti-P1 Antibodies
Anti-P1 Abs
Clinically Significant
occasionally
Abs class
IgM
Thermal range
4 – 22
Rare 22-37
HDNB
Yes
Transfusion Reactions
Extravascular
Intravascular No
Rare
Naturally occcurring Abs found in the serum of P2 Individuals

38. Clinically Significant Transfusion Reactions
Allo Anti-P Antibodies
Naturally occcurring Abs found in the serum of Pk and p Individuals
Allo Anti-P Abs
Clinically Significant
Yes
Abs class
IgM
Rare IgG
Thermal range
4 – 37S
HDNB
Rare
Transfusion Reactions
Extravascular
Intravascular No

39. Clinically Significant Transfusion Reactions
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 Abs
Clinically Significant
Yes
Abs class
IgG
Biphasic
Binds at 0
Hemolysis 37
HDNB
Rare
Transfusion Reactions
Extravascular
Intravascular

40. 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