TheKell antigen system (also known as theKell–Cellano system) is ahuman blood group system, that is, a group ofantigens on the human red blood cell surface which are important determinants ofblood type and are targets forautoimmune oralloimmune diseases which destroy red blood cells. The Kell antigens areK,k,Kp^a,Kp^b,Js^a andJs^b.^[1] The Kell antigens arepeptides found within theKell protein, a 93-kilodaltontransmembranezinc-dependentendopeptidase which is responsible for cleavingendothelin-3.^[2][3]

TheKEL gene encodes a type II transmembraneglycoprotein^[4] that is the highlypolymorphic Kell blood group antigen. The Kell glycoprotein links via a singledisulfide bond to theXK membrane protein^[5] that carries theKx antigen. The encoded protein contains sequence and structural similarity to members of theneprilysin (M13) family ofzincendopeptidases.^[6]

There are severalalleles of thegene which creates Kell protein. Two such alleles,K₁ (Kell) andK₂ (Cellano), are the most common. The kell protein is tightly bound to a second protein,XK, by adisulfide bond. Absence of the XK protein (such as throughgenetic 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 designatedCD238 (cluster of differentiation 238).

Kell antigens are important intransfusion medicine,autoimmune hemolytic anemia andhemolytic 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 developantibodies 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 associated with childbirth making Kell an important concern forhemolytic 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 ashemolysis. 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][9]}

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 resultinganemia. Similarly, a pregnant woman may develop antibodies against fetal red blood cells, resulting in destruction, anemia, andhydrops fetalis in a process known ashemolytic disease of the newborn (HDN). Both AIHA and HDN may be severe when caused by anti-Kell antibodies,^[10] as they are the most immunogenic antigens after those of theABO andRhesus blood group systems.^{[citation needed]}

McLeod phenotype (or McLeod syndrome) is anX-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]}

The Kell group was named after the first patient described with antibodies to K₁, a pregnant woman named Mrs. Kellacher in 1945.^[11] Mrs. Cellano was likewise a pregnant woman with the first described antibodies to K₂. The K₀phenotype was first described in 1957 and the McLeod phenotype was found in Hugh McLeod, aHarvard dental student, in 1961.^[12][13]KingHenry VIII of England may have had Kell-positive blood type, explaining the deaths of seven of his ten children at, or soon after, birth, supported by the revelation that Henry may have inherited Kell from his maternal great-grandmother,Jacquetta of Luxembourg.^[14] Alternatively he may have had McLeod syndrome, explaining his mental deterioration around age 40.^[15]

Evidence supports a genetic link between the Kell blood group (onchromosome 7 q33) and the ability to tastephenylthiocarbamide, or PTC, a bitter-tastingthiourea compound.^[16][17] Bitter taste receptor proteins in the taste buds of the tongue that recognise PTC are encoded on nearby chromosomelocus 7 q35-6.^{[citation needed]}

• 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 atBGMUT Blood Group Antigen Gene Mutation Database atNCBI,NIH
• KEL+protein,+human at the U.S. National Library of MedicineMedical Subject Headings (MeSH)

• Genes on human chromosome 7
• Clusters of differentiation
• Blood antigen systems
• Transfusion medicine

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