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Kell, Kx and Kidd Blood Group Systems
Kell and Kx Blood Group Systems
The Kell blood group system contains more than 34 antigens, although only one (K1) is of importance in routine practice. K1 is also commonly referred to as K, or incorrectly as “Kell,” as Kell is the name of the entire blood group system. Antigens are encoded by the KEL gene located on chromosome 7. They are found in the RBC membrane on a type 2 glycoprotein (CD238), are part of the zinc endopeptidase family and function as endothelium-3 convertases. Rare Ko (null) RBCs lack all Kell glycoprotein and all Kell system antigens. Individuals of this phenotype, however, have no obvious pathology. The Kell protein has a large extracellular C-terminal domain of 665 amino acids and a short N-terminal cytoplasmic domain ( Fig. 27.1 ). Kell antigens are destroyed by reducing agents such as dithiothreitol and 2-aminoethylisothiouronium bromide, which reduce the multiple intrachain disulfide bonds in the extracellular domain of the Kell protein; this characteristic is useful in antibody identification.
A related blood group system Kx, contains one antigen, Kx (XK1). This protein is encoded by the X-linked gene XK. Mutations in XK lead to severely reduced expression of Kell antigens, known as the McLeod phenotype, and neuromuscular abnormalities (described below). Kx is a 10-pass membrane-spanning protein that is linked to the Kell protein by a single disulfide bond and is essential for the expression of Kell system antigens. The Kx antigen is not usually exposed on the RBC, as that anti-Kx does not react with RBCs that carry normally expressed Kell antigens.
Antigens and Their Molecular Basis
The majority of Kell antigens are caused by nucleotide changes in KEL that cause single amino acid substitutions in the Kell protein. There are seven sets of high- and low-incidence antithetical antigens: K and k ; Kp a , Kp b , and Kp c ; Js a and Js b ; KEL11 and KEL17; KEL14 and KEL24; KEL25 and KEL28 ; and KEL31 and KEL38 (high-incidence antigens are in bold typeface). The polymorphisms associated with the most frequently considered Kell antigens are identified in Fig. 27.1 . There are also many other nonallelic low- and high-incidence antigens that are beyond the scope of this chapter. The prevalence of the commonly encountered Kell antigens differs by ethnic group: K+ is more common in Caucasian individuals and less often seen in those of African ancestry; Kp(a+b−) phenotype is almost always found in whites; and Js(a+b−) is almost exclusively found in individuals of African ethnicity ( Table 27.1 ). These prevalence data have relevance when searching for antigen-negative donor units and assessing antibody production in patients from different ethnic groups. Loss of Kell antigens, K 0 , results from various KEL mutations including nucleotide deletion, defective splicing, and premature stop codons. Mutations causing weak expression of Kell antigens are “Kell-mod” phenotypes.
Table 27.1
Kell Blood Group System Phenotypes and Prevalence
Modified from Hillyer, C. D., Strauss, R. G., & Luban, N. L. C. (Eds.). (2004). Handbook of pediatric transfusion medicine . San Diego, CA: Elsevier Academic Press.
| Phenotype | Prevalence (%) | |
|---|---|---|
| White | Blacks | |
| K–k+ | 91 | 98 |
| K+k+ | 8.8 | 2 |
| K+k– | 0.2 | Rare |
| Kp(a+b–) | Rare | 0 |
| Kp(a–b+) | 97.7 | 100 |
| Kp(a+b+) | 2.3 | Rare |
| Kp(a–b–c+) | 0.32 Japanese | 0 |
| Js(a+b–) | 0 | 1 |
| Js(a–b+) | 100 | 80 |
| Js(a+b+) | Rare | 19 |
McLeod Phenotype
The McLeod phenotype arises through deletions and mutations in XK , resulting in depressed expression of the Kell system antigens. Acanthocytic RBC morphology is sometimes present. McLeod syndrome, an X-linked condition affecting males, is a multisystem degenerative disorder. The syndrome encompasses a variety of muscular, neurological, and psychiatric defects, including skeletal muscle wasting, seizures, and cardiomyopathy. Symptoms can develop as late as the fourth decade of life. McLeod syndrome, thought to be underdiagnosed, has been reported in approximately 60 males worldwide. The phenotype can also be present in individuals with chronic granulomatous disease when there is a large chromosome X deletion that includes both the XK and the CYBB loci. These RBCs lack both Km and Kx antigens.
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