Kell blood group system most important blood group system following to ABO and Rh blood group system, particularly RhD as far as immunogenicity is concerned and Its clinical importance.

1. Kell Blood Group System
Dr. RAFIQ AHMAD, MBBS/MD, MTM, FSAP

2. Introduction
History
Nomenclature
Proteins/Genes and their functions
Antigens
Antibodies
Clinical Significance

3. Kell-History
First blood group antigen to be identified
after the discovery of antiglobulin test
(Coomb’s test).
KEL1 or K(Kelleher) identified in 1946
KEL2 or k(cellano) identified in 1949
Kpa , Kpb and K null phenotype discovered
in 1957.

4. Nomenclature
Number of Kell antigens: 35
ISBT symbol: KEL
ISBT number: 006
Gene symbol: KEL
 Gene name: Kell blood group
CD number CD238
In fetus Kell antigen appears very early
during erythropoiesis, K – 10 -11 week old
fetus, and k in 6 weeks old fetus

5. Kell Antigens
Number: 35
The K antigen is one of the most
clinically significant Kell antigens.
Specificity:
Protein: Amino acid sequence
determines the specificity of Kell
antigens

6. Kell Antigens
Antigen-carrying molecules:
Glycoprotein with enzymatic function
The Kell glycoprotein is a transmembrane,
single-pass protein that carries the Kell
antigens. It is an endothelin-3-converting
enzyme; it cleaves "big" endothelin-3 to
produce an active form that is a potent
vasoconstrictor

7. Kell Genetics
Gene-Chromosome 7q33
Name KEL
Organized into 19 exons of coding sequence
Product Kell glycoprotein
GENETICS: alleles K, k, Kpa , Kpb , Jsa ,
and Jsb are in "linkage disequilibrium"; no
gene exists which carries both K and Kpa or
Jsa , or both Kpa and Jsa . A. K/k, Kpa /Kpb
and Jsa /Jsb inherited in autosomal,
codominant fashion.
 McLeod syndrome is inherited in X-linked
fashion.

8. Kell Genetics
Molecular basis:
The KEL gene encodes the Kell antigens.
KEL is highly polymorphic. It has two
major codominant alleles, k and K, which
result from a SNP (698C→T), and the
corresponding k and K antigens differ by a
single amino acid change (T193M).

9. Kell Frequencies
 ~100%: k, Kpb, Ku, Jsb, K11, K12, K13, K14, K18,
K19, Km, K22, K26, K27
K antigen: 2% in Blacks, 9% in Caucasians, up
to 25% in Arabs
~2%: Kpa, U1a
~0.01%: Jsa (0.01% in Caucasians, 20% in Blacks),
Kpc, K23
Others: K17 (~0.3%), K24 (rare), VLAN (rare), K16
(unknown)
 K-k+ in 91% Caucasians and 98% Blacks
ANTIGENIC STRUCTURE:
 Kell antigens located on red cell membrane
glycoprotein(CD238)
 4- 5 N-glycans present; no O glycosylation

10. Kell Antigens

11. Kell Antigen- Its Functions
Kell glycoprotein is an endothelin-3-converting
enzyme (big endothelins- ET3--
vasoconstriction)
Kell glycoprotein is a memberof the Neprilysin
(M13) sub-family of zinc endopeptidases and has
sequence and structural homology with neutral
endopeptidase,(CALLA,enkephalinase) and
endothelin-converting enzyme ECE-1.

12. Kell structure – Xk
Kell linked to Xk protein through a disulfide bond
Xk –integral membrane protein which expresses
the Kx blood group antigen(XK1) .
XK gene encoding Kx antigen is located on X
chromosome at Xp21.1 ,as a separate blood group
system

13. Onset of expression of the components of
the Kell blood group complex
 Expression of both Kell and XK is limited to the
erythroid lineage,expression of Kell, but not of XK,
was noted in bipotent erythroid- megakaryocyte
progenitors.
 Thus the expression of Kell and XK is independent,
and this is in keeping with previous studies, with
transfected cells, that showed that coexpression of
Kell and XK is not necessary for transport of the
proteins to the cell surface - Jeffrey et al .,
TRANSFUSION,2005

14. Phenotype
Caucasians
Percentage
African- American
Percentage
RBB Dammam
k 91 98 90%
K+k+ 8.8 2 9.1%
K 0.2 RARE 0.9%
Kp a RARE 0 0.1%
Kp b 97.7 100 100%
Kp(a+b+) 2.3 RARE -
Kp c 0.32 0 -
Js(a+b-) 0 1 -
Js(a-b+) 100 80 -

15. Kell Antigens
 KELL 1(K): low incidence antigen, 9% whites .3.5%
in blacks .
 KELL 2(k):
High incidence antigen in all populations
This polymorphism arises due to SNP in exon 6,
Met193Thr

16. KELL antigens
Kpa(KEL3):
2%whites NOT IN BLACKS
Kpb( KEL4):It is the common allele, the codon is
CGG.
Kpa/ Kpb /Kpc differ from the common allele by
single base change in the same codon in exon 8,
TGG and CAG respectively.
Js a(KEL6): confined to African ethnicity
16% prevalence

17. Other KELL antigens
Low prevalence antigens: Ul a, K23, KYO(single
amino acid substitution)
High prevalence antigens :
k, Kpb,Jsb, K11,K14
OTHER HIGH INCIDENCE ANTIGEN:
K12, K13, K18,K19,K22,TOU, RAZ,KALT, KTIM

18. Kx antigen
Expressed most strongly on red cells that
lack Kell antigens, ie., K0 red cells
Only antigen in Kx system
X linked recessive gene Xk at Xp21
BLOOD GROUP SYSTEM:019
A part of dimeric amino acid transporter,
covalent linkage to type 2 membrane Kell
glycoprotein

19. K null (K0) and Kmod phenotypes
K0:
No kell antigens detectable in RBC
Immunised individuals produce anti-Ku
(anti-KEL5)
Anti Ku – recognises universal Kell antigen (Ku)on all
cells, except K0
Might be by nonsense/missense/splice site mutations
It has single specificity , can cause both HDFN and
hemolytic reactions

20. Kmod phenotype
Kmod is an inherited rare RBC phenotype
characterized by weak but detectable expressionof
high-incidence Kell antigens
Homozygous or heterozygous for missense
mutations in kell glycoprotein
Some produce anti Ku,but nonreactive with Kmod
cells

21. Mcleod phenotype- serology
They can make 2 alloantibodies after
transfusion– anti KL , mixture of anti Kx
and anti Km.
Km antigen is found in all red cells other
than K0 red cells /Mcleod phenotype.

22. LyonizationI-McLeod phenotype
Mixed populations of Kx+ and Kx– red cells, or of red
cells with strong and weak Kell antigen expression are
recognized in many female carriers of genes
responsible for the McLeod phenotype.
The proportion of McLeod phenotype red cells in
female McLeod carriers usually varies from 5% to
85% .
This dual population is often difficult to detect
serologically, especially if Kell antibodies and not
anti-Kx are used, but flow cytometry permits an
accurate estimationof the two red cell populations

23. McLeod phenotype
All Kell antigens are depressed ,Xk absent on red
cells
Deletion of that part of the chromosome containing
Xk
Minority of X linked CGD have this phenotype
includes the deletion of locus for a X linked GD
and Xk locus
Clinical features:

25. Mcleod Syndrome
Clinical features:
Acanthocytic red cells, elevated CK ,
Other muscular and neurological
defects.

26. Weak expression of Kell antigens
Other inherited causes for weak expression of kell
phenotype
when glycophorin C and D are absent (Leach
phenotype);
 when a portion of the extracellular domain of
glycophorin Cand D, specifically exon 3, is
deleted (some Gerbich negative phenotypes).
Acquired causes: AIHA, ITP, microbial infection

27. Tissue expression
Kell protein detected in testis ,skeletal
muscle, lymphoid tissues
Not found in WBCs or platelets

28. Action of Enzymes on Kell Antigens
Papain
Ficin Resistant
Trypsin
Alpha chymotripsin
2ME/ DTT/ AET
Mixture of trypsin Sensitive
and chymotrypsin

29. Effect of Enzymes
Enhanced antibody activity:
Cleavage of glycoprotein leads to:
Decreased activity :
Cleavage of glycoprotein leads to
1.Reduces the negative
charge on
RBC
2.Reduces the steric
hindrance
3.Making cells more
hydrophobic
It is seen in Rh, Kidd, P,
lewis, I
antigens
loss of antigens ,
it is seen in Fy a, Fyb, MNS
systems

30. Kell Antibodies-Anti- K
Anti K and anti k Usually IgG ( IgG1)
Causes severe HDFN and HTR
Anti K -the most common immune red cell
antibody other than ABO/Rh system
Most anti K appears due to blood
transfusion, few are due to microbial
infection ,few in healthy donors
K is less immunogenic than D

31. Kell antibodies
Anti K found in 1/1000 pregnant women
Incidence of HDFN due to anti K -1/20000
pregnancies
The frequency of HDFN due to anti K is lower
as the mother is immunised by transfusion not by
pregnancy
In most cases fetus is K negative
HDN due to anti K severe when immunization is
due to previous pregnancy

32. K-HDFN Pathogenesis
 Kell glycoprotein appears earlier in erythropoiesis than
D antigens
 Anti K induced phagocytosis of K+ erythroid
progenitors
FEATURES:
1. Lower levels of reticulocytes /AF bilirubin /
erythroblasts
2. Less severe post natal hyperbilirubinemia
3. Treatment: recombinant erythropoietin

33. K-HDFN Management
There is no correlation between antibody titer and
degree of inhibition
Neonates with Kell HDFN require less
phototherapy and exchange transfusions.
Because of the destruction of red cell precursor
cells as well, treatment with erythropoietin may be
more effective in neonates with Kell HDFN
compared to Rh HDFN

34. Other antibodies
Anti k cause severe hemolytic
reactions, but less common
Anti Kpb is an auto antibody in AIHA
anti Js a,anti Js b are rare, causing
DHTRs
Anti Ku in K0 individuals, reacts with
all samples except K0

35. The End!!
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