Kell antigen system
| Kell protein | |
|---|---|
| Identifiers | |
| Symbol | KEL |
| Entrez | 3792 |
| HUGO | 6308 |
| OMIM | 110900 |
| RefSeq | NM_000420 |
| UniProt | P23276 |
| Other data | |
| Locus | Chr. 7 q33 |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
The Kell antigen system (also known as Kell-Cellano system) is a group of antigens on the human red blood cell surface which are important determinants of blood type and are targets for autoimmune or alloimmune diseases which destroy red blood cells. The Kell antigens are peptides found within the kell protein, a 93 kilodalton transmembrane zinc-dependent endopeptidase which is responsible for cleaving endothelin-3.[1][2]
There are several alleles of the gene which creates Kell protein. Two such alleles, K1 (Kell) and K2 (Cellano), are the most common. The kell protein is tightly bound to a second protein, XK, by a disulfide bond. Absence of the XK protein (such as through genetic deletion), leads to marked reduction of the Kell antigens on the red blood cell surface. Absence of the Kell protein (K0), however, does not affect the XK protein.[3]
Disease association
Kell antigens are important in transfusion medicine, autoimmune hemolytic anemia, and hemolytic disease of the newborn. Individuals lacking a specific Kell antigen may develop antibodies against Kell antigens when transfused with blood containing that antigen. Subsequent blood transfusions may be marked by destruction of the new cells by these antibodies, a process known as hemolysis. People without Kell antigens(K0), must be transfused with blood from donors who are also K0 to prevent hemolysis.
Autoimmune hemolytic anemia (AIHA) occurs when the body produces an antibody against a blood group antigen on its own red blood cells. The antibodies lead to destruction of the red blood cells with resulting anemia. Similarly, a pregnant woman may develop antibodies against fetal red blood cells, resulting in destruction, anemia, and hydrops fetalis in a process known as hemolytic disease of the newborn (HDN). Both AIHA and HDN may be severe when caused by anti-Kell antibodies,[4] as they are the most immunogenic antigens after those of the ABO and Rhesus blood group systems.
McLeod phenotype
McLeod phenotype (or McLeod syndrome) is an X-linked anomaly of the Kell blood group system in which Kell antigens are poorly detected by laboratory tests. The McLeod gene encodes the XK protein, a protein with structural characteristics of a membrane transport protein but an unknown function. The XK appears to be required for proper synthesis or presentation of the Kell antigens on the red blood cell surface.
History
The Kell group was named after the first patient described with antibodies to K1, a pregnant woman named Mrs. Kellacher in 1945.[5] Mrs. Cellano was likewise a pregnant woman with the first described antibodies to K2. The K0 phenotype was first described in 1957 and the McLeod phenotype was found in Hugh McLeod, a Harvard dental student, in 1961. [6][7]
Other associations
Evidence supports a genetic link between the Kell blood group (on chromosome 7 q33) and the ability to taste phenylthiocarbamide, or PTC, a bitter-tasting thiourea compound. [8] [9] Bitter taste receptor proteins in the taste buds of the tongue that recognise PTC are encoded on nearby chromosome locus 7 q35-6.
References
- Online Mendelian Inheritance in Man (OMIM) 110900 - OMIM entry for Kell protein
- Online Mendelian Inheritance in Man (OMIM) 314850 - OMIM entry for XK protein
- ↑ Lee S, Wu X, Reid M, Zelinski T, Redman C. Molecular basis of the Kell (K1) phenotype. Blood. 1995 Feb 15;85(4):912-6. PMID 7849312
- ↑ Lee S, Lin M, Mele A, Cao Y, Farmar J, Russo D, Redman C. Proteolytic processing of big endothelin-3 by the kell blood group protein. Blood. 1999 Aug 15;94(4):1440-50. PMID 10438732
- ↑ Yu LC, Twu YC, Chang CY, Lin M. Molecular basis of the Kell-null phenotype: a mutation at the splice site of human KEL gene abolishes the expression of Kell blood group antigens. J Biol Chem. 2001 Mar 30;276(13):10247-52. Epub 2000 Dec 27. PMID 11134029
- ↑ Wiener CP, and Widness JA. Decreased fetal erythropoiesis and hemolysis in Kell hemolytic anemia. American Journal of Obstetrics and Gynecology. 1996 174: 547-55 PMID 8623782
- ↑ Coombs RRA, Mourant AE, Race RR. A new test for the detection of weak and incomplete Rh agglutinins. Br J Exp Pathol 1945;26:255
- ↑ Chown B, Lewis M, Kaita K. A new Kell blood-group phenotype. Nature. 1957 Oct 5;180(4588):711. PMID 13860532
- ↑ Allen FH Jr, Krabbe SM, Corcoran PA. A new phenotype (McLeod) in the Kell blood-group system. Vox Sang. 1961 Sep;6:555-60. PMID 13477267
- ↑ Crandall BF, Spence MA. Linkage relations of the phenylthiocarbamide locus (PTC). Hum Hered. 1974;24(3):247-52.PMID 4435792
- ↑ Conneally PM, Dumont-Driscoll M, Huntzinger RS, Nance WE, Jackson CE. Linkage relations of the loci for Kell and phenylthiocarbamide taste sensitivity. Hum Hered. 1976;26(4):267-71. PMID 976995
External links
- Kell at BGMUT Blood Group Antigen Gene Mutation Database at NCBI, NIH