Molecular basis of two novel and related high‐prevalence antigens in the Kell blood group system, KUCI and KANT, and their serologic and spatial association with K11 and KETI

Abstract

Background The numerous antigens in the Kell blood group system result from missense nucleotide changes in KEL. Antibodies to antigens in this system can be clinically important. We describe six probands whose plasma contained antibodies to high-prevalence Kell antigens, and discuss their relationship. Study design and methods PCR amplification, direct sequencing, RFLP assays, hemagglutination, flow cytometry, and protein modeling were performed by standard methods. Results Proband 1 (KUCI), and her serologically-compatible sister, were heterozygous for a nucleotide change in exon 11 (KEL*1271C/T; Ala424Val). Proband 2 (KANT) was heterozygous for KEL*1283G/T (Arg428Leu) and KEL*1216C/T (Arg406Stop) in exon 11. RBCs from Proband 1 and her sister were not agglutinated by plasma from Proband 2; however, RBCs from Proband 2 were agglutinated by plasma from Proband 1. Probands 3, 4, 5, and 6 had the KEL*1391C>T change associated with the previously reported KETI− phenotype. Proband 5 was also homozygous for KEL*905T>C encoding the K11−K17+ phenotype. Hemagglutination studies revealed an association between KUCI, KANT, KETI and K11. Protein modeling indicated that whereas Ala424 and Arg428 are clustered, Val302 and Thr464 are not. Conclusion Ala424 in the Kell glycoprotein is associated with the high-prevalence Kell antigen, KUCI (ISBT 006032), which is detected by the antibody of Proband 1. Arg428 is associated with the high-prevalence Kell antigen, KANT (ISBT 006033). The association between KUCI, KANT, KETI, and K11, and the results of protein modeling are discussed.

Three novel alleles in the Kell blood group system resulting in the Knull phenotype and the first in a Native American

“…The presence of alloanti‐Ku in the plasma from Proband 1 confirms that the allele is silenced even though we could not identify the cause. Thus, Proband 1 joins the increasing number of probands who have one silenced KEL allele by a mechanism not revealed by sequencing all 19 KEL exons and their flanking intronic regions …”

Expansion of the Kell blood group system: two new high‐prevalence antigens and two novel K0 (Kellnull) phenotypes

“…We and others have previously encountered examples of people who lack high‐prevalence Kell antigens other than Kp b , yet present with anti‐Kp b . Velliquette and colleagues reported a KETI−, Kp(b+) proband who initially had made anti‐Kp b . The specificity later changed to anti‐KETI.…”

Flow cytometry in transfusion medicine: an overview

“…Various antibodies to specific antigens, as well as anti-CD238, an antibody towards the complete glycoprotein, have been used for elucidating weak expression, new antigens and K O phenotypes. Velliquette et al [23] used flow cytometry in the elucidation of high-prevalence antigens in the Kell blood group system. In a Dutch study, Ji et al [24] examined a large cohort of donors for antigen variants in the Kell blood group system.…”

“…Velliquette et al . used flow cytometry in the elucidation of high‐prevalence antigens in the Kell blood group system. In a Dutch study, Ji et al .…”