CBGs + Kell and Kx Flashcards
The CBGs include:
• Kell Blood Group System
• Duffy Blood Group System
• Kidd Blood Group System
• Lutheran Blood Group System
The Kell Blood Group System (ISBT???) and Kx Blood Group System (ISBT???) are closely linked but are genetically distinct.
006
019
Discovery of Kell and Kx
• Year:
• Discovered by:
1946
Kelleher
The____ system is similar to the Rh system in that it has high-incidence and low-incidence antigens.
Kell
How Many Antigens Are in the Kell System?
• Harmening’s Book: Mentions 32 antigens.
• Other Books: List 35 or 37 antigens.
Genetics of Kell System
• Gene:
• Location:
• Function:
KEL gene
Chromosome 7
Produces K and k antigens
Antigen K
Former Name
Alternative Name
Discovery Order
Incidence in Population
Kell
KEL 1 antigen
First
<9% (low incidence)
Antigen k
Former Name
Alternative Name
Discovery Order
Incidence in Population
Cellano (formerly Nocella)
KEL 2 antigen
Second
>90% (high incidence)
• One of the most immunogenic antigens after Rh(D).
K Antigen (KEL 1)
This blood group system was the first to be discovered using anti-human globulin (AHG) testing.
Kell
is clinically significant and can cause severe hemolytic transfusion reactions and HDFN.
Anti-K
KELL ANTIGENS
Antigens are well developed at birth
10 weeks of gestation
Detectable on red cell of the baby
7 weeks of gestation (developed earlier)
Found on RBC of the baby inside the womb
K (9%)
k (99.8%)
suppresses erythropoiesis (red blood cell production), leading to severe anemia in Hemolytic Disease of the Fetus and Newborn (HDFN).
Anti-K
Once Anti-K is produced, the patient can only be safely transfused with …
K -negative blood.
Solution for Rare Kell Phenotypes:
Autologous Donation
Kpa Antigen
Other Name
Frequency
(KEL3) PENNEY
2% (low-frequency antigen
Kpb Antigen
Other Name
Frequency
(KEL4) RAUTENBERG
99.9% (high-frequency antigen)
Kpc Antigen
Other Name
Frequency
None
Very rare
Jsa Antigen
Other Name
Frequency
(KEL6) SUTER
20% in Blacks,
0.1% in Whites (very rare in Whites)
Jsb Antigen
Other Name
Frequency
(KEL7) MATTHEWS
80-100% (high-frequency antigen)
is more common in Black populations (20%) but very rare in Whites (0.1%).
Jsa (SUTER)
• Kell antigens are located on the_____
• The_____ gene (found on chromosome 7) is responsible for coding the Kell glycoprotein.
Kell glycoprotein.
KEL gene
KEL glycoprotein is composed of______ aa
730 amino acids
Kell glycoprotein
Membrane Interaction
- Traverses the red blood cell (RBC) membrane_____
Cysteine Content
Contains____ cysteine residues
Bonds
- Each cysteine forms a _____with another cysteine
Function of the Bonds
- Provides…
once
15
disulfide bond
… structural stability by folding the Kell glycoprotein into its 3D shape
Some references describe the Kell antigen as a “______” because of the network of disulfide bonds forming a unique shape.
Kel Cloud
KEL Gene Type
~ Normal KEL Gene
Kell Antigens Expressed
All high-incidence antigens (k, Jsb, Kpb) are present
KEL Gene Type
~ Mutated KEL Gene
Kell Antigens Expressed
One high-incidence antigen is replaced by a low-incidence antigen (e.g., K, Jsa, Kpa)
The Kx glycoprotein is encoded by the_____ gene, which is located on the______.
XK gene
X chromsome
The______ is encoded by the XK gene, which is located on the X chromosome.
Kx glycoprotein
Responsible for the maintenance of the red blood cell’s membrane integrity
• Able to maintain the shape and deformability of the red cell membrane
Kx glycoprotein
• Absence of ____= RBC membrane deformability
Kx
A cysteine molecule from the Kx glycoprotein forms a disulfide bond with the cysteine molecule from Kell glycoprotein due to close proximity
forms:______
Km antigen
universal Kell antigen
• always present when there is a Kell glycoprotein
Ku antigen
Km Antigen
Formed by the disulfide bond between a____ and _____
Kx cysteine and a Kell cysteine
Universal Kell antigen, always present if Kell glycoprotein is present
Ku Antigen (KEL5)
Why Are Kell Antigens Resistant to Enzyme Treatment?
• Kell antigens have_______ bonds, which make them resistant to proteolytic enzymes like (2)
disulfide-bonded
papain and ficin.
Kell antigens
Resistant to enzyme treatment (papain, ficin)
But can be destroyed with the combination of (2)
trypsin and chymotrypsin
Kell antigens
Sensitive to SULFHYDRYL REAGENTS
Due to the disulfide bonds (5)
• 2-mercaptoethanol (2-ME)
• Dithiothreitol (DTT)
• 2-aminoethyl isothiouronium bromide (AET)
• ZZAP (DTT + enzyme)
• glycine-acid EDTA
sulfhydryl reagents can also destroy other antibodies from other blood groups: (5)
Lutheran
Lewis
Dombrock
Cromer
Knops
lacking the expression of all Kell antigens(including Ku) on the red cell membrane except Kx
due to the inheritance of double dose of amorph KEL gene (Ko gene)
Kell NULL
is a silent Kell allele resulting in the null phenotype in which there is no expression of Kell antigens except a related antigen called Kx
K0 gene
•____ normally helps maintain RBC shape and flexibility.
• Kell-null RBCs do not fully lose their shape because____ is still present.
• However, if it is also absent, severe membrane deformability occurs.
Kell
Kx
Produced by Kellnull individuals
• Can cause HDFN & HTR (clinically significant)
Anti-Ku (KEL5)
• _____ is an antibody produced by Kell-null (Ko) individuals.
• Since Ku is a universal Kell antigen, people with Kell-null phenotype see Ku as foreign and produce Anti-Ku
Anti-Ku
• Kell-null individuals require rare Kell-negative blood for transfusion.
• If no Kell-null (Ko) blood is available, artificial Kell-null cells can be created using (2)
DTT or sulfhydryl agents.
How Are Artificial Kell-Null Cells Created?
1. Treat normal RBCs with_____
2. It destroys_____, removing all Kell antigens.
3. These cells become safe for transfusion into Kell-null individuals with Anti-Ku.
DTT (or other sulfhydryl reagents)
Kell glycoprotein
- Kell glycoprotein is coded by the____ gene on chromosome___ and traverses the RBC membrane once.
- It contains___ cysteine residues that form strong disulfide bonds, stabilizing the antigen structure.
- Kx glycoprotein (encoded by___ gene on___ chromosome) is closely linked to Kell and maintains RBC integrity
KEL; 7
15
XK; X
- Kell antigens are resistant to _____but can be destroyed by____
- ______individuals lack all Kell antigens and produce____, requiring rare Kell-negative blood.
- If Kell-null blood is unavailable, normal RBCs can be treated with____ to artificially remove Kell antigens.
papain/ficin; sulfhydryl reagents (DTT, AET, ZZAP).
Kell-null (Ko); Anti-Ku
DTT
• is primarily IgG and reacts well at the AHG (antihuman globulin) phase.
• Rarely, Anti-K can be IgM, which is associated with infections.
Anti-K
Anti-K
Potentiator
LISS
Polyethylene Glycol
Activity of Anti-K(IgG)???
LISS - reduced
PEG - increased
Anti-K
IgM form (rare) is associated with cases of infection (EEMMCC)
E. coli 0125:B15
Enterococcus faecalis
Mycobacteria
Morganella morganii
Campylobacter jejuni
Campylobacter coli
Anti-K
May react as_____
Some samples were able to agglutinate red cells that were suspended in saline
Immediate Spin phase
Anti-K Found in a Newborn
• A newborn was found to have Anti-K in serum, but the mother lacked Anti-K.
• Normally, babies cannot produce their own blood group antibodies at birth.
• Reason: ???
• Justification: When the baby recovered, IgM Anti-K disappeared, proving its association with the infection.
The baby was infected with E. coli O125:B15, which has a K-like antigen that stimulated IgM Anti-K production.
is the most common Kell antibody because K antigen is highly immunogenic (strong at stimulating an immune response).
Anti-K
ACTIVITY IN RELATION TO HDFN
ANTI-K
• Suppression of erythropoiesis
• Reticulocytopenia
• Anemia
ACTIVITY IN RELATION TO HDFN
ANTI-D
Hemolysis
Reticulocytosis
Hyperbilirubinemia
Anemia
ANTI-K and ANTI-D
similarities
SIMILARITY
Both are non-efficient in activating the complement system.
Majority of the hemolysis that occurs happen extravascularly.
reacts to younger or immature forms of RBC since K antigens are already expressed on red cells as early as 10 weeks gestation
• ANTI-K
______reacts to mature red cells
Presence of this leads to hemolysis → reticulocytosis (compensatory mechanism in response to hemolysis) → hyperbilirubinemia (since red cells already contain hemoglobin, bilirubin is a byproduct of its degradation) → anemia
ANTI-D
If you have_____, RBCs will not reach its mature form → suppression of erythropoeisis (result of destruction during proerythroblast stage) → reticulocytopenia → anemia
Anti-K
• k (Cellano)
• Kpb
• Jsb
PROBLEM: masks other antigens that may be present on the red cell
RESOLUTION: treatment with…
sulfhydryl reagents (DTT,
2-mercaptoethanol, etc)
• ______ are low-incidence Kell antigens.
• Since they are rare, few individuals have them, meaning antibodies against them are rarely found
Kpa and Jsa
_____suppresses erythropoiesis, leading to fetal anemia (reticulocytopenia), whereas ____causes hemolysis (reticulocytosis, hyperbilirubinemia).
Anti-K
Anti-D
Kx ANTIGEN
ISBT___;
019
membrane transport protein
Kx antigen
Kx antigen
Produced by the____ gene is located____ chromosome
XK1
X
Kx antigen
Present in all RBCs except…
Mcleod phenotype
Mcleod phenotype
phenotype for those individuals who are lacking____ antigen-> absence of___ gene.
Kx
XK1
Kell (+)
• Kx antigens are…
Kell (-) / Ko/null
• Kx antigens are…
Present in all small amounts
increased
Individuals with the_____ lack Kx antigen and have weakened Kell antigen expression.
McLeod phenotype
- The Kx antigen normally plays a role in maintaining RBC shape and deformability.
- Without Kx, Kell glycoproteins are unstable and cannot properly interact with the RBC membrane.
- This leads to abnormal RBC shapes (_____) and reduced cell flexibility, making RBCs prone to destruction.
- The result is a chronic hemolytic anemia, in which RBCs break down prematurely.
acanthocytosis
McLeod Syndrome
First discovered from a dental student named______ in which his rbcs appeared to be Ko but were able to demonstrate weak expressions of the high incidence antigens of Kell group system
Hugh Mcleod
• McLeod Syndrome results from a mutation or deletion of the___ gene, which is responsible for producing the___ antigen.
• The XK1 gene is located on the___ chromosome.
• When XK1 is deleted or mutated, Kx antigen is completely absent.
• This absence suppresses the expression of Kell antigens on the RBC surface.
• Since Kx antigen helps maintain RBC membrane integrity, its absence leads to abnormal RBC morphology and reduced RBC lifespan.
XK1; Kx
X
• CYBB gene, which encodes a component of NADPH oxidase, is also located on the X chromosome, very close to XK1.
• If there is a deletion of XK1, the nearby CYBB gene may also be deleted.
• This dual deletion leads to both the McLeod phenotype and CGD, resulting in McLeod Syndrome.
