CBGs + Kell and Kx Flashcards by Kyra Catedral

The CBGs include:

• Kell Blood Group System
• Duffy Blood Group System
• Kidd Blood Group System
• Lutheran Blood Group System

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The Kell Blood Group System (ISBT???) and Kx Blood Group System (ISBT???) are closely linked but are genetically distinct.

006

019

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Discovery of Kell and Kx
• Year:
• Discovered by:

1946

Kelleher

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The____ system is similar to the Rh system in that it has high-incidence and low-incidence antigens.

Kell

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How Many Antigens Are in the Kell System?

• Harmening’s Book: Mentions 32 antigens.
• Other Books: List 35 or 37 antigens.

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Genetics of Kell System
• Gene:
• Location:
• Function:

KEL gene

Chromosome 7

Produces K and k antigens

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Antigen K

Former Name
Alternative Name
Discovery Order
Incidence in Population

Kell
KEL 1 antigen
First
<9% (low incidence)

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Antigen k

Former Name
Alternative Name
Discovery Order
Incidence in Population

Cellano (formerly Nocella)
KEL 2 antigen
Second
>90% (high incidence)

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• One of the most immunogenic antigens after Rh(D).

K Antigen (KEL 1)

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This blood group system was the first to be discovered using anti-human globulin (AHG) testing.

Kell

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is clinically significant and can cause severe hemolytic transfusion reactions and HDFN.

Anti-K

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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%)

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suppresses erythropoiesis (red blood cell production), leading to severe anemia in Hemolytic Disease of the Fetus and Newborn (HDFN).

Anti-K

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Once Anti-K is produced, the patient can only be safely transfused with …

K -negative blood.

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Solution for Rare Kell Phenotypes:

Autologous Donation

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Kpa Antigen

Other Name
Frequency

(KEL3) PENNEY

2% (low-frequency antigen

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Kpb Antigen

Other Name
Frequency

(KEL4) RAUTENBERG

99.9% (high-frequency antigen)

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Kpc Antigen

Other Name
Frequency

None
Very rare

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Jsa Antigen

Other Name
Frequency

(KEL6) SUTER

20% in Blacks,
0.1% in Whites (very rare in Whites)

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Jsb Antigen

Other Name
Frequency

(KEL7) MATTHEWS

80-100% (high-frequency antigen)

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is more common in Black populations (20%) but very rare in Whites (0.1%).

Jsa (SUTER)

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• Kell antigens are located on the_____

• The_____ gene (found on chromosome 7) is responsible for coding the Kell glycoprotein.

Kell glycoprotein.

KEL gene

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KEL glycoprotein is composed of______ aa

730 amino acids

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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

disulfide bond

… structural stability by folding the Kell glycoprotein into its 3D shape

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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

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

1. Kell glycoprotein is coded by the____ gene on chromosome___ and traverses the RBC membrane once. 2. It contains___ cysteine residues that form strong disulfide bonds, stabilizing the antigen structure. 3. Kx glycoprotein (encoded by___ gene on___ chromosome) is closely linked to Kell and maintains RBC integrity

KEL; 7 15 XK; X

4. Kell antigens are resistant to _____but can be destroyed by____ 5. ______individuals lack all Kell antigens and produce____, requiring rare Kell-negative blood. 6. 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

1. The Kx antigen normally plays a role in maintaining RBC shape and deformability. 2. Without Kx, Kell glycoproteins are unstable and cannot properly interact with the RBC membrane. 3. This leads to abnormal RBC shapes (_____) and reduced cell flexibility, making RBCs prone to destruction. 4. 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.

CBGs + Kell and Kx Flashcards

(76 cards)