Kell antigen system
Encyclopedia
The Kell antigen system (also known as Kell-Cellano system) is a group of antigen
s 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.
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
endopeptidase
s.
There are several allele
s 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).
, autoimmune hemolytic anemia
and hemolytic disease of the newborn (anti-Kell)
. 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, as they are the most immunogenic antigens after those of the ABO
and Rhesus blood group system
s.
was first described in 1957 and the McLeod phenotype was found in Hugh McLeod, a Harvard dental student, in 1961.
, 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.
Antigen
An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...
s on the human red blood cell surface which are important determinants of blood type
Blood type
A blood type is a classification of blood based on the presence or absence of inherited antigenic substances on the surface of red blood cells . These antigens may be proteins, carbohydrates, glycoproteins, or glycolipids, depending on the blood group system...
and are targets for autoimmune
Autoimmune disease
Autoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. In other words, the body actually attacks its own cells. The immune system mistakes some part of the body as a pathogen and attacks it. This may be restricted to...
or alloimmune
Alloimmunity
Alloimmunity is a condition in which the body gains immunity against antigens of another individual of the same species, which are perceived as foreign....
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
Zinc
Zinc , or spelter , is a metallic chemical element; it has the symbol Zn and atomic number 30. It is the first element in group 12 of the periodic table. Zinc is, in some respects, chemically similar to magnesium, because its ion is of similar size and its only common oxidation state is +2...
-dependent endopeptidase
Endopeptidase
Endopeptidase or endoproteinase are proteolytic peptidases that break peptide bonds of nonterminal amino acids , in contrast to exopeptidases, which break peptide bonds from their end-pieces. For this reason, endopeptidases cannot break down peptides into monomers, while exopeptidases can break...
which is responsible for cleaving endothelin-3.
Protein
The KEL gene encodes a type II transmembrane glycoproteinGlycoprotein
Glycoproteins are proteins that contain oligosaccharide chains covalently attached to polypeptide side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. In proteins that have segments extending...
that is the highly polymorphic Kell blood group antigen. The Kell glycoprotein links via a single disulfide bond
Disulfide bond
In chemistry, a disulfide bond is a covalent bond, usually derived by the coupling of two thiol groups. The linkage is also called an SS-bond or disulfide bridge. The overall connectivity is therefore R-S-S-R. The terminology is widely used in biochemistry...
to the XK membrane protein
XK (protein)
XK is a protein found on human red blood cells and other tissues which is responsible for the Kx antigen which helps determine a person's blood type.-Clinical significance:...
that carries the Kx antigen. The encoded protein contains sequence and structural similarity to members of the neprilysin
Neprilysin
Neprilysin, also known as membrane metallo-endopeptidase, neutral endopeptidase , CD10, and common acute lymphoblastic leukemia antigen , is a zinc-dependent metalloprotease enzyme that degrades a number of small secreted peptides, most notably the amyloid beta peptide whose abnormal misfolding and...
(M13) family of zinc
Zinc
Zinc , or spelter , is a metallic chemical element; it has the symbol Zn and atomic number 30. It is the first element in group 12 of the periodic table. Zinc is, in some respects, chemically similar to magnesium, because its ion is of similar size and its only common oxidation state is +2...
endopeptidase
Endopeptidase
Endopeptidase or endoproteinase are proteolytic peptidases that break peptide bonds of nonterminal amino acids , in contrast to exopeptidases, which break peptide bonds from their end-pieces. For this reason, endopeptidases cannot break down peptides into monomers, while exopeptidases can break...
s.
There are several allele
Allele
An allele is one of two or more forms of a gene or a genetic locus . "Allel" is an abbreviation of allelomorph. Sometimes, different alleles can result in different observable phenotypic traits, such as different pigmentation...
s of the gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
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
XK (protein)
XK is a protein found on human red blood cells and other tissues which is responsible for the Kx antigen which helps determine a person's blood type.-Clinical significance:...
, by a disulfide bond
Disulfide bond
In chemistry, a disulfide bond is a covalent bond, usually derived by the coupling of two thiol groups. The linkage is also called an SS-bond or disulfide bridge. The overall connectivity is therefore R-S-S-R. The terminology is widely used in biochemistry...
. Absence of the XK protein (such as through genetic deletion
Genetic deletion
In genetics, a deletion is a mutation in which a part of a chromosome or a sequence of DNA is missing. Deletion is the loss of genetic material. Any number of nucleotides can be deleted, from a single base to an entire piece of chromosome...
), 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
Cluster of differentiation
The cluster of differentiation is a protocol used for the identification and investigation of cell surface molecules present on white blood cells, providing targets for immunophenotyping of cells...
238).
Disease association
Kell antigens are important in transfusion medicineTransfusion medicine
Transfusion medicine is the branch of medicine that is concerned with the transfusion of blood and blood components. The blood bank is the section of the clinical laboratory where medical technologists process and distribute blood products under the supervision of a medical director, often...
, autoimmune hemolytic anemia
Autoimmune hemolytic anemia
Autoimmune hemolytic anemia occurs when antibodies directed against the person's own red blood cells cause the RBCs to burst , leading to insufficient plasma concentration. The lifetime of the RBCs is reduced from the normal 100–120 days to just a few days in serious cases...
and hemolytic disease of the newborn (anti-Kell)
Hemolytic disease of the newborn (anti-Kell)
Hemolytic disease of the newborn is the second most common cause of severe hemolytic diseases of newborns after Rh disease. Anti-Kell1 is becoming relatively more important as prevention of Rh disease is also becoming more effective....
. Individuals lacking a specific Kell antigen may develop antibodies
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
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
Hemolysis
Hemolysis —from the Greek meaning "blood" and meaning a "loosing", "setting free" or "releasing"—is the rupturing of erythrocytes and the release of their contents into surrounding fluid...
. People without Kell antigens(K0), must be transfused with blood from donors who are also K0 to prevent hemolysis.
Autoimmune hemolytic anemia
Autoimmune hemolytic anemia
Autoimmune hemolytic anemia occurs when antibodies directed against the person's own red blood cells cause the RBCs to burst , leading to insufficient plasma concentration. The lifetime of the RBCs is reduced from the normal 100–120 days to just a few days in serious cases...
(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
Anemia
Anemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
. Similarly, a pregnant woman may develop antibodies against fetal red blood cells, resulting in destruction, anemia, and hydrops fetalis
Hydrops fetalis
Hydrops fetalis is a condition in the fetus characterized by an accumulation of fluid, or edema, in at least two fetal compartments. By comparison, hydrops allantois or hydrops amnion are an accumulation of excessive fluid in the allantoic or amniotic space respectively.-Presentation:Locations can...
in a process known as hemolytic disease of the newborn
Hemolytic disease of the newborn (anti-Kell)
Hemolytic disease of the newborn is the second most common cause of severe hemolytic diseases of newborns after Rh disease. Anti-Kell1 is becoming relatively more important as prevention of Rh disease is also becoming more effective....
(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
ABO blood group system
The ABO blood group system is the most important blood type system in human blood transfusion. The associated anti-A antibodies and anti-B antibodies are usually IgM antibodies, which are usually produced in the first years of life by sensitization to environmental substances such as food,...
and Rhesus blood group system
Rhesus blood group system
The Rh blood group system is one of thirty current human blood group systems. Clinically, it is the most important blood group system after ABO. At Present, the Rh blood group system consists of 50 defined blood-group antigens, among which the 5 antigens D, C, c, E, and e are the most important...
s.
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. Mrs. Cellano was likewise a pregnant woman with the first described antibodies to K2. The K0 phenotypePhenotype
A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...
was first described in 1957 and the McLeod phenotype was found in Hugh McLeod, a Harvard dental student, in 1961.
Other associations
Evidence supports a genetic link between the Kell blood group (on chromosome 7 q33) and the ability to taste phenylthiocarbamidePhenylthiocarbamide
Phenylthiocarbamide, also known as PTC, or phenylthiourea,is an organosulfur thiourea containing a phenyl ring.It has the unusual property that it either tastes very bitter or is virtually tasteless, depending on the genetic makeup of the taster...
, or PTC, a bitter-tasting thiourea
Thiourea
Thiourea is an organosulfur compound of with the formula SC2 . It is structurally similar to urea, except that the oxygen atom is replaced by a sulfur atom, but the properties of urea and thiourea differ significantly. Thiourea is a reagent in organic synthesis. "Thioureas" refers to a broad...
compound. Bitter taste receptor proteins in the taste buds of the tongue that recognise PTC are encoded on nearby chromosome locus
Locus (genetics)
In the fields of genetics and genetic computation, a locus is the specific location of a gene or DNA sequence on a chromosome. A variant of the DNA sequence at a given locus is called an allele. The ordered list of loci known for a particular genome is called a genetic map...
7 q35-6.
External links
- OMIM entry for Kell protein - OMIM entry for XK protein- Kell at BGMUTBGMUTThe BGMUT Database documents allelic variations in the genes encoding for human blood group systems. It was set up in 1999 through an initiative of the Human Genome Variation Society . Since 2006, it has been a part of the dbRBC resource of NCBI at the NIH...
Blood Group Antigen Gene Mutation Database at NCBINational Center for Biotechnology InformationThe National Center for Biotechnology Information is part of the United States National Library of Medicine , a branch of the National Institutes of Health. The NCBI is located in Bethesda, Maryland and was founded in 1988 through legislation sponsored by Senator Claude Pepper...
, NIH