Blood Group--Kell System

A number sign (#) is used with this entry because more than 25 antigens of the Kell blood group system are determined by variation in the KEL gene on chromosome 7q33 (KEL; 613883). A single antigen, Kx, is carried by the XK gene (314850) on chromosome Xp21.

Description

The Kell blood group system is formed by 2 disulfide-linked proteins, Kell and XK. The Kell protein is a type II membrane glycoprotein sharing sequence homology with members of the M13 family of zinc-dependent metalloproteases and possessing enzymatic activity characteristic of that group (summary by Claperon et al., 2007).

The Kell blood group system is highly polymorphic, expressing over 25 antigens that have been classified in to 5 antithetical sets of high and low prevalence antigens with the others being independently expressed or having unknown antithetical partners. The different phenotypes are due to single-nucleotide mutations that result in an amino acid substitution (summary by Sha et al., 2006). See, for example, Kell (designated K or K1)/Cellano (k, K2) (T193M; 613883.0001).

Yu et al. (2001) noted that the Kell antigens are the most potent immunogens aside from the A and B antigens of the ABO system (616093) and the D antigen (111680) of the Rh system (see 111700).

Clinical Features

K1 is a strong immunogen; its antibodies can cause severe reactions if incompatible blood is transfused and may cause hemolytic disease of the newborn of sensitized mothers (summary by Lee et al., 1995). Newborns with hemolytic anemia caused by anti-Kell antibodies present signs of suppressed erythropoiesis, suggesting that anti-Kell antibodies suppress erythropoiesis at the progenitor level (summary by Camara-Clayette et al., 2001). Consequently, neither maternal antibody titers nor amniotic bilirubin levels are good predictors of the severity of the disease (summary by Westhoff and Reid, 2004).

The lack of Kell antigens, K(0), can be caused by several different gene defects. K-null individuals do not have any obvious defect (summary by Westhoff and Reid, 2004).

Weakened Kell antigens and absence of the Kx antigen at the surface of red blood cells define the McLeod phenotype (300842). Although this phenotype is related to Kell, it is the Kx antigen which is either deleted or mutated and no longer able to bind Kell (summary by Claperon et al., 2007). While K-null red cells have no detectable Kell surface antigens, an enhanced level of Kx antigens differentiates the K-null from the McLeod phenotype (summary by Westhoff and Reid, 2004). The McLeod phenotype also includes acanthocytosis and neurologic abnormalities.

Population Genetics

Kell antigens show population variations. K has an incidence of 9% in Caucasians but is much less common in other ethnic backgrounds (summary by Westhoff and Reid, 2004). The KEL6 antigen (see 613883.0003) has an incidence of 20% in persons of African heritage but occurs in only about 1% of Caucasians (summary by Lee et al., 2003). Although it is very rare, the K-null phenotype is widely distributed and has been identified in Europeans, Japanese, Africans, and Indians (summary by Yu et al., 2001).

Mapping

Conneally et al. (1974, 1976) found Kell and PTC (171200) to be closely linked: total lod = 10.78 at theta = 0.045. Keats et al. (1978) raised the question of linkage of Kell and PTC to Jk-Km-Co, then thought to be on chromosome 7. Spence et al. (1984) analyzed 2 new datasets regarding PTC/Kell linkage and found a maximum likelihood estimate for theta (both sexes) of 0.28. All published data including these gave a combined maximum likelihood estimate of 0.14 (lod = 8.94) but there was statistically significant evidence of heterogeneity among the published studies.

History

The Kell and Cellano blood groups are symbolized K and k, respectively. The Kell-Cellano system illustrates nicely the manner in which the understanding of several of the blood group systems has developed. Sutter is part of the Kell system (VAM).

Linkage data, suggestive but not conclusive, on Kell and pepsinogen (169700) were reported by Weitkamp et al. (1975).

Westhoff and Reid (2004) summarized the history of the Kell/Kx blood group system. The Kell blood group system was discovered in 1946, just a few weeks after the introduction of the antiglobulin test. The red blood cells of a newborn baby, thought to be suffering from hemolytic disease of the newborn (HDN), gave a positive reaction in the direct antiglobulin test (DAT). The serum of the mother reacted with red blood cells from her husband and her older child and was later shown to react with 9% of random donors. The system was named from Kelleher, her surname, and the antigen is referred to as K (Kell, K1). Three years later, the antithetical antigen, k (Cellano, K2), which is of high incidence in all populations, was identified by typing large numbers of red blood cell samples with an antibody that had also caused mild HDN (Levine et al., 1949).