Blood group systems

2. Kell Blood Group System

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

4. 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 Knull phenotype discovered in
1957.

5. 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,
- k in 6 weeks old fetus

6. 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

7. 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

8. Kell Genetics
Gene-Chromosome 7q33
Name KEL
Organized into 19 exons of coding
sequence
Product Kell glycoprotein
. K/k, Kpa /Kpb and Jsa /Jsb inherited
in autosomal, codominant fashion.

9. 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).

10. 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
~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

12. Kell Antigens

13. 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

14. 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

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. Knull (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

22. 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.

24. McLeod phenotype
All Kell antigens are depressed ,Xk absent on
red cells
Deletion of that part of the chromosome
containing Xk
Red cell morphological and functional
abnormalities characterized by:
Decreased red cell survival
Reticulocytosis

25. Mcleod Syndrome
McLeod phenotype is just on phenomenon
attributed to Mcleod Syndrome.
Acanthocytic red cells, elevated CK ,
Other muscular and neurological defects.
The x-linked disorder of chronic granuolomatous
disease is occasionally associated with Mcleod
Syndrome.

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

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

30. 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

31. 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
Produced in response to antigen expousure
through blood transfusion or pregnancy ,
few are due to microbial infection ( IgM).
K is less immunogenic than D

32. Kell antibodies
Anti K found in 1/1000 pregnant women
Incidence of HDFN due to anti K -1/20000
pregnancies
In most cases fetus is K negative
HDN due to anti K severe when immunization is
due to previous pregnancy

33. 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

34. 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

35. 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

36. The End!!
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