The Expanding Kell Blood Group System and its Relation to Chronic Granulomatous Disease

Abstract

The Kell blood group, which presently includes 18 associated antigens, can now be seen as a system of considerable complexity. Most of the antigenic specificities reflect different mutational sites in the structural region of the Kell autosomal gene, but the product of an X-linked gene is also involved in the expression of Kell. The X-linked gene, called X<sup>1</sup>k, is believed to direct synthesis of a precursor substance, named Kx, which is utilized by the Kell gene for production of Kell antigens. K<sub>o</sub> (K null) red cells are homozygous for amorphic Kell genes and lack all Kell antigens, but they have a great excess of unconverted Kx substance. The K antigen has high immunogenicity and about 10 percent of K negative people who are given one unit of K positive blood make anti-K. Rare examples of naturally occurring Kell antibodies are found. One such antibody, present in an untransfused 20 day old child, has been associated with production of a soluble K-like antigen by a coliform organism in the intestinal tract. A number of Kell phenotypes are characterized by weak antigenicity, the most important of these being the McLeod type which has X-linked inheritance and has been found only in males. McLeod red cells lack Kx antigen, a deficiency that is associated with marked changes in red cell morphology. Leukocytes do not have recognizable amounts of Kell antigens but neutrophil leukocytes and monocytes have strong Kx activity. Leukocytes of boys with X-linked chronic granulomatous disease lack Kx antigen, an aberration that appears to be one of a primary nature and not a secondary effect of the disease. Some of these patients have red cells of the McLeod phenotype. Three rare variant alleles at the Xk locus (X<sup>2</sup>k, X<sup>3</sup>k and X<sup>4</sup>k) are postulated to direct the different permutations of Kx synthesis that have been recognized on leukocytes and red cells. Lack of leukocyte Kx antigen is associated with a defect in bactericidal function while lack of red cell Kx is associated with abnormal morphology and the McLeod phenotype.