Characterization of Jk(a+(weak)): a new blood group phenotype associated with an altered JK*01 allele.

BACKGROUND

The clinically important Kidd (JK) blood group system is considered to be relatively uncomplicated, both serologically and genetically. The JK01 and JK02 alleles give rise to Jk(a) and Jk(b) antigens, respectively, and silenced alleles result in Jk(a-b-). Other inherited variants analogous to Fy(x) and weak D phenotypes have not been characterized for JK, although recent abstracts indicate their presence.

STUDY DESIGN AND METHODS

Six index samples from individuals whose RBCs reacted variably or weakly with different sources of anti-Jk(a) and 300 controls of the four known JK phenotypes were investigated by standard serology, flow cytometry, Western blotting, and the urea hemolysis test. Molecular analysis, including allele-specific polymerase chain reaction (PCR), DNA sequencing, and transcript analysis by real-time PCR, was performed.

RESULTS

All Jk(a+(w)b-) and Jk(a+(w)b+) index samples were homo- or heterozygous for an altered JK01 allele carrying 130G>A (Glu44Lys) and the JK02-associated silent SNPs 588G and Intron 9 -46g. Blood donor screening indicated an allele frequency of 0.042. Titration and flow cytometry with anti-Jk(a) gave lower values in index samples compared to controls, as did anti-Jk3 titers. Donors with 130A also showed significantly decreased Jk(a) density by flow cytometry versus 130G. Western blotting with anti-UT-B demonstrated weaker reactivity with Jk(a+(w)) membranes while JK mRNA levels could not discriminate index samples from controls. The urea hemolysis test was only moderately affected in two Jk(a+(w)b-) samples.

CONCLUSIONS

A new phenotype with weakened Jk(a) expression on RBCs is associated with a JK*01-like allele, which may constitute a risk for hemolytic transfusion reactions if antigen-positive units are missed by routine serology.