Kell antigen system
|Alt. symbols||ECE3, CD238|
|Locus||Chr. 7 q33|
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. Kell can be noted as K, k, or Kp. The Kell antigens are peptides found within the Kell protein, a 93 kilodalton transmembrane zinc-dependent endopeptidase which is responsible for cleaving endothelin-3.
The KEL gene encodes a type II transmembrane glycoprotein that is the highly polymorphic Kell blood group antigen. The Kell glycoprotein links via a single disulfide bond to the XK membrane protein that carries the Kx antigen. The encoded protein contains sequence and structural similarity to members of the neprilysin (M13) family of zinc endopeptidases.
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.
The Kell protein has also recently been designated CD238 (cluster of differentiation 238).
Kell antigens are important in transfusion medicine, autoimmune hemolytic anemia and hemolytic disease of the newborn (anti-Kell). Anti-K is the next most common immune red cell antibody after those in the ABO and Rh system. Anti-K typically presents as IgG class alloantibody. Individuals lacking a specific Kell antigen may develop antibodies against Kell antigens when transfused with blood containing that antigen. This is particularly true for the "K" antigen which shows a relatively high antigenicity and moderately low frequency (~9%) in Caucasian populations. Anti-K can also occur following transplacental hemorrhage (TPH) associated with childbirth making Kell an important concern for hemolytic disease of the newborn. Following the formation of anti-K, subsequent blood transfusions may be marked by destruction of the new cells by these antibodies, a process known as hemolysis. Anti-K does not bind complement, therefore hemolysis is extravascular. Individuals without K antigens(K0) who have formed an antibody to a K antigen, 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, as they are the most immunogenic antigens after those of the ABO and Rhesus blood group systems.
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.
The Kell group was named after the first patient described with antibodies to K1, a pregnant woman named Mrs. Kellacher in 1945. 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. There is recent information speculating that King Henry VIII of England had Kell positive blood type, explaining the deaths of seven of his ten children at, or soon after, birth. His mental deterioration around age 40 could be explained by McLeod Syndrome. (See Philippa Gregory, "The King's Curse", Simon & Schuster, 2014, pages 602-603.)
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. Bitter taste receptor proteins in the taste buds of the tongue that recognise PTC are encoded on nearby chromosome locus 7 q35-6.
- Kaita H, Lewis M, Chown B, Gard E (June 1959). "A further example of the Kell blood group phenotype K-,k-,Kp(a-b-)". Nature 183 (4675): 1586. doi:10.1038/1831586b0. PMID 13666821.
- Dean L. "The Kell blood group -- Blood Groups and Red Cell Antigens". NCBI Bookshelf. National Center for Biotechnology Information - United States National Institutes of Health. Retrieved 2009-05-04.
- Lee S, Wu X, Reid M, Zelinski T, Redman C (1995). "Molecular basis of the Kell (K1) phenotype". Blood 85 (4): 912–6. PMID 7849312.
- Lee S, Lin M, Mele A, Cao Y, Farmar J, Russo D, Redman C (1999). "Proteolytic processing of big endothelin-3 by the kell blood group protein". Blood 94 (4): 1440–50. PMID 10438732.
- "Entrez Gene: KEL".
- Yu LC, Twu YC, Chang CY, Lin M (2001). "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. 276 (13): 10247–52. doi:10.1074/jbc.M009879200. PMID 11134029.
- Weiner CP, Widness JA (1996). "Decreased fetal erythropoiesis and hemolysis in Kell hemolytic anemia". Am. J. Obstet. Gynecol. 174 (2): 547–51. doi:10.1016/S0002-9378(96)70425-8. 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 (1957). "A new Kell blood-group phenotype". Nature 180 (4588): 711. doi:10.1038/180711a0. PMID 13477267.
- Allen FH Jr, Krabbe SM, Corcoran PA (1961). "A new phenotype (McLeod) in the Kell blood-group system". Vox Sang. 6 (5): 555–60. doi:10.1111/j.1423-0410.1961.tb03203.x. PMID 13860532.
- Crandall BF, Spence MA (1974). "Linkage relations of the phenylthiocarbamide locus (PTC)". Hum. Hered. 24 (3): 247–52. doi:10.1159/000152657. PMID 4435792.
- Conneally PM, Dumont-Driscoll M, Huntzinger RS, Nance WE, Jackson CE (1976). "Linkage relations of the loci for Kell and phenylthiocarbamide taste sensitivity". Hum. Hered. 26 (4): 267–71. doi:10.1159/000152813. PMID 976995.
- Online 'Mendelian Inheritance in Man' (OMIM) 110900 - OMIM entry for Kell protein
- Online 'Mendelian Inheritance in Man' (OMIM) 314850 - OMIM entry for XK protein
- Kell at BGMUT Blood Group Antigen Gene Mutation Database at NCBI, NIH
- KEL protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)