MIDTERM LECTURE 1: KELL BLOOD GROUP Flashcards
Who were the Kell blood group system and anti-K named after? And year.
Mrs. Kelleher, whose serum contained the first identified example of anti-K
When was anti-K first identified?
1946
What is the antithetical partner to K, and when was it discovered?
k, discovered in 1949
Which Kell antigens were described in 1957 and 1958?
Kpa (1957) and Kpb (1958)
What are the antithetical partners discovered in the Kell system in 1958 and 1963?
Jsa (1958) and Jsb (1963).
What discovery in 1957 helped associate more antigens with the Kell system?
The identification of the null phenotype, Ko
How many antigens are included in the Kell blood group system?
36
What ISBT symbol and number are assigned to the Kell blood group system?
KEL, 006
Which antigen is the only one in the Kx system?
Kx
Where are Kell blood group antigens found?
only RBCs
Which associated protein is found in erythroid and other tissues like the brain, heart, and skeletal muscle?
Xk protein
At what stage of fetal development can K and k antigens be detected?
K at 10 weeks, k at 7 weeks.
How many K antigen sites are found per RBC?
Between 3,500 and 18,000.
Which enzyme treatments destroy Kell antigens?
Trypsin and chymotrypsin when used together.
Enzyme that do not destroy Kell antigens
ficin and papain
Which substances destroy Kell antigens but not Kx?
Thiol-reducing agents such as DTT, 2-ME, AET, and ZZAP.
How many sets of antithetical Kell antigens exist?
8
Which Kell antigen is more prevalent in certain populations?
Jsb
Which testing method led to the discovery of the Kell blood group system?
Antiglobulin testing
Why is K considered highly immunogenic despite its low quantity on RBCs?
Because even a small amount of K antigen can strongly stimulate an immune response.
Which IgG-removal agent destroys Kell antigens?
glycine-acid EDTA
Why is the Kell system important in transfusion medicine?
Because Kell antigens are highly immunogenic and can cause severe transfusion reactions and hemolytic disease of the fetus and newborn (HDFN).
What makes the Kell system different from other blood group systems?
It was the first system discovered after antiglobulin testing, and its antigens are only found on RBCs, unlike other systems that also appear on different tissues.
What happens if the Kx protein is absent or defective?
It can lead to McLeod syndrome, a rare condition affecting RBCs, muscles, and the nervous system.
How immunogenic is the K antigen compared to other blood group antigens?
Excluding the ABO system, K is second only to D in immunogenicity.
What are the primary ways anti-K antibodies develop?
through pregnancy and blood transfusion
How common is the K antigen?
Found in 9% of whites, making K+ transfusions rare.
How rare are anti-k antibodies?
Extremely rare; only 2 in 1,000 lack k antigen.
What are Kpa and Kpc?
Low-prevalence mutations of Kpb
How does anti-K react in testing? Immunoglobulin class.
Mostly IgG, detected via IAT; PEG enhances detection.
How does anti-K cause hemolytic disease of the fetus and newborn (HDFN)?
Unlike Rh antibodies, anti-K suppresses erythropoiesis by targeting erythroid precursor cells in the fetal bone marrow.
What is the Kell glycoprotein?
731-amino acid protein, spans RBC membrane, linked to Xk protein.
chromosome of KEL gene
chromosome 7 (7q33)
chromosome of XK gene
X chromosome (Xp21.1)
Ko phenotype can develop what antibody
anti-Ku
anti-Ku react with what RBCs
all but Ko RBCs
What causes McLeod syndrome?
Mutations or deletions in the XK gene, which encodes the Kx antigen.
McLeod phenotype symptoms
Acanthocytosis, hemolytic anemia, neuro disorders, cardiomyopathy.
McLeod phenotype can be linked to what disorder
Chronic Granulomatous Disease
How does McLeod inheritance work?
X-linked; female carriers have two RBC populations (Lyon hypothesis).
How does McLeod affect Kell antigen expression?
Weak expression of all Kell antigens; no Kx, Km.
rare Ko (Kell-null) phenotype antigens
no Kell antigens but increased Kx antigen expression
What is the most common Kell phenotype?
K-k+ (K-negative, k-positive)
Which Kell antigens have high vs. low prevalence?
High-prevalence: k (Cellano), Kpb, Jsb, Ku
Low-prevalence: K (Kell), Kpa, Jsa
T or F:
anti-K can cause HTR
T
(delayed and acute)
Which potentiator enhances anti-K detection?
PEG (polyethylene glycol)
What is the Kmod phenotype?
variant with weakened Kell antigen expression, caused by mutations in KEL or XK genes.
who discorvered McLeod phenotype
Allen and coworkers described a male medical student with weak Kell antigen expression in 1961
What type of anemia do McLeod individuals have?
chronic hemolytic anemia
What lab findings suggest McLeod phenotype anemia?
Reticulocytosis, bilirubinemia, splenomegaly, and reduced serum haptoglobin levels.
What is a key enzyme marker elevated in McLeod syndrome?
Serum creatinine phosphokinase (CK-MM) and carbonic anhydrase III.
what is CGD
immune disorder where phagocytes lack NADH oxidase making them unable to produce hydrogen peroxide (H₂O₂) for bacterial killing.
Do all McLeod individuals have CGD?
No, not all McLeod males have CGD, and not all CGD patients have McLeod phenotype.
Why do some McLeod individuals have CGD?
The XK gene is adjacent to the CYBB gene (which encodes NADPH oxidase)
What antibodies are produced by McLeod individuals with CGD?
Anti-Kx + Km (sometimes called anti-KL)
anti-KL reacts strongly with what RBCs
Ko RBCs
What antibody is made by McLeod individuals without CGD?
Anti-Km
What specialized test can confirm McLeod phenotype?
Flow cytometry to detect missing Kx antigen.
How do McLeod RBCs react to enzyme treatment?
Not affected by proteolytic enzymes (papain, ficin, trypsin, bromelain), but destroyed by DTT and AET.
What conditions are associated with weaker-than-normal Kell antigen expression?
1) McLeod phenotype
2) Suppression by the Kpa gene (cis-modified effect)
3) Gerbich-negative phenotypes (Ge: –2, –3, 4 and Ge: –2, –3, –4)
4) Kmod phenotypes
How does the Kpa gene suppress Kell antigen expression?
It has a cis-modifying effect
cis-modifying effect in Kell antigen expression means
it weakens Kell antigen expression only on the same chromosome.
What is the relationship between Gerbich-negative phenotypes and Kell antigens?
Gerbich-negative RBCs show depressed Kell antigen expression
What is the term used for other phenotypes with very weak Kell antigen expression?
Kmod
What happens to Kx antigen expression in Kmod phenotypes?
enhanced compared to normal RBCs
How do Kmod individuals differ from Ko individuals in antibody production?
Kmod individuals may make an antibody similar to anti-Ku, but it does not react with other Kmod RBCs.
whose case study demonstrated the bacterial acquisition of Kell antigens?
McGinnis et al
what did McGinnis discover related to bacterial acquisition of Kell antigens
described a K-negative patient who developed a K-like antigen during a Streptococcus faecium infection.
Which specific Kell antigens have been reported as targets of autoantibodies?
K, Kpb, and K13
first blood group system discovered after the introduction of antiglobulin testing
Kell
