Transfusion medicine
Red blood cell antigens
Kell system
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PubMed Search: Transfusion[TIAB] Kell[TI] group
Table of Contents
Definition / general | Essential features | Antigens | Antibodies | Terminology | Clinical features | Transmission | Case reports | Additional references | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Adkins BD, Booth GS. Kell system. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/transfusionmedkellgroup.html. Accessed April 18th, 2024.
Definition / general
- Highly immunogenic
- Antibodies clinically significant
Essential features
- Most Kell antigens are widely expressed on the surface of red blood cells in the donor population
- Antibodies can cause hemolysis and hemolytic disease of the fetus and newborn (HDFN)
- Kell is expressed in early erythroid precursors, which can lead to suppression of erythropoiesis in the fetus
Antigens
- Type: peptides found within the Kell protein (CD238); the Kell blood group antigens are expressed on a large transmembrane protein with extensive disulfide bonds; the function of this protein is unknown (AABB: Technical Manual, 19th Edition, 2017)
- 36 antigens total (AABB: Technical Manual, 19th Edition, 2017)
- K or KEL1, often referred to erroneously as Kell antigen, is highly immunogenic but has low prevalence; it is encoded by the KEL gene on chromosome 7 (AABB: Technical Manual, 19th Edition, 2017)
- k or K2 (archaic Cellano), is a high prevalence antigen; it is a codominant allele and can be expressed alongside KEL1 (AABB: Technical Manual, 19th Edition, 2017)
- Many Kell antigens are expressed in high frequency amongst the donor population, specifically k, Jsb, Kpb and Ku; K (KEL1), is expressed less frequently and often matched in sickle cell disease patients due to its high immunogenicity
- Kell antigens are destroyed by dithiothreitol treatment, which is commonly used when evaluating panels for patients on daratumumab; as such, patients on daratumumab must undergo phenotyping prior to drug administration or genotyping in order to provide Kell matched red blood cell products, as antibodies cannot be identified by routine methods
- Kx is a protein associated with Kell antigens required for normal expression on red cells; absence of Kx, which is encoded by the XK gene, leads to decreased expression of Kell antigens, acanthocytosis and the clinical presentation of McLeod phenotype (AABB: Technical Manual, 19th Edition, 2017)
- Kell null phenotype arises in individuals inheriting defective KEL gene (K0) and may form Ku antibodies; Kell null red cells have no expression of Kell antigens but increased levels of Kx
Table 1: prevalence of KEL phenotypes
| White | 91 | 8.8 | 0.2 | 97.7 | 2.3 | Rare | 100 | Rare | 0 |
| African American (US) | 98 | 2 | Rare | 100 | Rare | 0 | 80 | 19 | 1 |
Antibodies
- Majority IgG, fewer IgM (AABB: Technical Manual, 19th Edition, 2017)
- Occurs with transfusion, pregnancy or activities such as intravenous drug use
- Can cause hemolytic reactions and hemolytic disease of the fetus and newborn
- Kell antigens are expressed in early erythropoiesis so there is immune clearance of red cell precursors; this leads to severe anemia without significant fetal hemolysis
- Kell null individuals can develop antibodies against Ku, a high frequency Kell antigen and subsequently require blood from other K0 (Kell null) individuals
- Not generally affected by dosage and unaffected by enzyme treatment
Terminology
- K or KEL1
- k or K2 (archaic Cellano)
Clinical features
- McLeod syndrome is an X-linked disease characterized by neuromuscular symptoms, such as cognitive abnormalities, movement disorders and psychiatric symptomology and ongoing hemolytic anemia; caused by an absence of the Xk protein (which expresses the Kx antigen) (GeneReviews: McLeod Neuroacanthocytosis Syndrome [Accessed 25 November 2020])
- The gene responsible for X-linked Chronic Granulomatous Disease is near the XK gene on the X chromosome and may be also be lost in patients presenting with McLeod phenotype (Blood: Chronic Granulomatous Disease and Mcleod Syndrome: Single Center Report of Four Cases [Accessed 11 February 2021])
Transmission
- Exposure to Kell antigens secondary to pregnancy or transfusion
Case reports
- 59 year old woman with a history of lymphoma developed a Kpa alloantibody (Asian J Transfus Sci 2018;12:81)
- 66 year old man with McLeod syndrome (BMC Neurol 2019;19:301)
- 66 year old man with the first description of an anti-Ku antibody in Korea (Korean J Lab Med 2009;29:238)
- Atypical presentation of hemolytic disease of the fetus and newborn in a Kell null mother (Transfus Med Hemother 2017;44:53)
- Anti-K1 antibody present in breast milk (Case Rep Pediatr 2017;2017:6927813)
Additional references
Board review style question #1
Which group of antigens is expressed early in erythropoiesis, leading to hemolytic disease of the fetus and newborn without significant hemolysis?
- Duffy
- Kell
- Lutheran
- Rh
Board review style answer #1
B. Kell. Erythropoiesis is inhibited in the fetus by binding of Kell antigens, which are expressed on early erythroid precursors. (N Engl J Med 1998;338:798)
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Reference: Kell group
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Reference: Kell group
Board review style question #2
Kell antigens have a high prevalence in the donor population. Which Kell antigen is expressed by almost all donors?
- K1
- K2
- Kpa
- Ku
Board review style answer #2
D. Ku. Ku or universal is expressed by the majority of the donor population. Of note, many Kell antigens are high frequency antigens such as k, Jsb and Kpb. K (KEL1) is less frequently expressed (~9%) but highly immunogenic.
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Reference: Kell group
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