Kell antigen system
| Kell protein | |||||||
|---|---|---|---|---|---|---|---|
| Identifiers | |||||||
| Symbol | KEL | ||||||
| Alt. symbols | ECE3, CD238 | ||||||
| NCBI gene | 3792 | ||||||
| HGNC | 6308 | ||||||
| OMIM | 110900 | ||||||
| RefSeq | NM_000420 | ||||||
| UniProt | P23276 | ||||||
| Other data | |||||||
| Locus | Chr. 7 q33 | ||||||
| |||||||
The Kell antigen system (also known as the Kell–Cellano system) is a human blood group system, that 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 K, k, Kpa, Kpb, Jsa and Jsb.[1] The Kell antigens are peptides found within the Kell protein, a 93-kilodalton transmembrane zinc-dependent endopeptidase which is responsible for cleaving endothelin-3.[2][3]
Protein
[edit]The KEL gene encodes a type II transmembrane glycoprotein[4] that is the highly polymorphic Kell blood group antigen. The Kell glycoprotein links via a single disulfide bond to the XK membrane protein[5] that carries the Kx antigen. The encoded protein contains sequence and structural similarity to members of the neprilysin (M13) family of zinc endopeptidases.[6]
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 or through a single point mutation within the coding region of the XK gene[7]), 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.[8]
The Kell protein has also recently been designated CD238 (cluster of differentiation 238).
Disease association
[edit]
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.[citation needed]
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,[9] as they are the most immunogenic antigens after those of the ABO and Rhesus blood group systems.[citation needed]
McLeod phenotype
[edit]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 of unknown function. The XK appears to be required for proper synthesis or presentation of the Kell antigens on the red blood cell surface.[citation needed]
History
[edit]The Kell group was named after the first patient described with antibodies to K1, a pregnant woman named Mrs. Kellacher in 1945.[10] 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.[11][12] King Henry VIII of England may have had Kell-positive blood type, explaining the deaths of seven of his ten children at, or soon after, birth, and suggesting that his mental deterioration around age 40 could be explained by McLeod Syndrome;[13] this was supported by the revelation that Henry may have inherited Kell from his maternal great-grandmother, Jacquetta of Luxembourg.[14]
Other associations
[edit]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.[15][16] Bitter taste receptor proteins in the taste buds of the tongue that recognise PTC are encoded on nearby chromosome locus 7 q35-6.[citation needed]
References
[edit]- ^ Smart, E.; Armstrong, B. (2008). "Blood group systems". ISBT Science Series. 3 (2): 68–92. doi:10.1111/j.1751-2824.2008.00188.x. ISSN 1751-2816.
- ^ Lee S, Wu X, Reid M, Zelinski T, Redman C (February 1995). "Molecular basis of the Kell (K1) phenotype". Blood. 85 (4): 912–6. doi:10.1182/blood.V85.4.912.bloodjournal854912. PMID 7849312.
- ^ Lee S, Lin M, Mele A, Cao Y, Farmar J, Russo D, Redman C (August 1999). "Proteolytic processing of big endothelin-3 by the kell blood group protein". Blood. 94 (4): 1440–50. doi:10.1182/blood.V94.4.1440. PMID 10438732. Archived from the original on 2013-04-14.
- ^ Russo DC, Lee S, Reid M, Redman CM. Topology of Kell blood group protein and the expression of multiple antigens by transfected cells. Blood. 1994 Nov 15;84(10):3518-23.
- ^ Russo DC, Redman C, Lee S. Association of XK and Kell blood group proteins. J Biol Chem. 1998 May 29;273(22):13950-6.
- ^ "Entrez Gene: KEL".
- ^ Russo DC, Lee S, Reid ME, Redman CM (Mar 2002). "Point mutations causing the McLeod phenotype". Transfusion. 42 (3): 287–93. doi:10.1046/j.1537-2995.2002.00049.x. PMID 11961232. S2CID 41663851.
- ^ Yu LC, Twu YC, Chang CY, Lin M (March 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". The Journal of Biological Chemistry. 276 (13): 10247–52. doi:10.1074/jbc.M009879200. PMID 11134029.
- ^ Weiner CP, Widness JA (February 1996). "Decreased fetal erythropoiesis and hemolysis in Kell hemolytic anemia". American Journal of Obstetrics and Gynecology. 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 (October 1957). "A new Kell blood-group phenotype". Nature. 180 (4588): 711. Bibcode:1957Natur.180..711C. doi:10.1038/180711a0. PMID 13477267. S2CID 4187507.
- ^ Allen FH, Krabbe SM, Corcoran PA (September 1961). "A new phenotype (McLeod) in the Kell blood-group system". Vox Sanguinis. 6 (5): 555–60. doi:10.1111/j.1423-0410.1961.tb03203.x. PMID 13860532. S2CID 30275809.
- ^ Whitley CB, Kramer K (December 2010). "A new explanation for the reproductive woes and midlife decline of Henry VIII". The Historical Journal. 53 (4): 827–848. doi:10.1017/S0018246X10000452. S2CID 159499333.
- ^ Stride P, Lopes Floro K (2013). "Henry VIII, McLeod syndrome and Jacquetta's curse". The Journal of the Royal College of Physicians of Edinburgh. 43 (4): 353–60. doi:10.4997/JRCPE.2013.417. PMID 24350322.
- ^ Crandall BF, Spence MA (1974). "Linkage relations of the phenylthiocarbamide locus (PTC)". Human Heredity. 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". Human Heredity. 26 (4): 267–71. doi:10.1159/000152813. PMID 976995.
External links
[edit]- 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 U.S. National Library of Medicine Medical Subject Headings (MeSH)