LQCL2615 - CMLE - A Case of the Weakened Jka Allele-LQCL2615

LQCL2615 - Educational Activity

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This document reviews the molecular and serologic complexity of the Kidd (JK) blood group system and highlights how molecular diagnostics can resolve discrepant transfusion-testing results. Kidd antigens Jka (JK*01) and Jkb (JK*02) are encoded by the SLC14A1 gene, which produces the UT-B urea transporter expressed on red blood cells and in multiple tissues. The common Jka/Jkb difference is driven by a single SNP at nucleotide 838, causing an amino acid substitution that leads to codominant antigen expression. Clinically, Kidd antibodies (anti-Jka, anti-Jkb, and especially anti-Jk3 in Kidd-null individuals) are important causes of hemolytic transfusion reactions—often delayed—and may be weak, dosage-dependent, and sometimes best detected by sensitive methods such as solid-phase red cell adherence testing.<br /><br />A case is presented in which a patient developed anti-Jka despite typing as Jka-positive, an unexpected finding that raised concern for a variant allele or altered antigen expression. The document contrasts true Kidd-null phenotypes (often due to silent/null alleles such as the Polynesian splice-site mutation c.342-1G>A in JK*B) with weak-expression phenotypes that can mimic null status and complicate serologic typing.<br /><br />Key emphasis is placed on the weakened Jka allele JK*01W (including JK*01W.01), defined by a missense mutation c.130G>A (p.Glu44Lys) along with associated silent polymorphisms. Studies using serology, flow cytometry, western blotting, urea lysis testing, allele-specific PCR, and Sanger sequencing show that JK*01W causes reduced UT-B/Jka expression despite normal mRNA levels, implying a post-transcriptional/protein effect. In the case resolution, genotyping identified the patient as JK*01W.01/JK*02, explaining weak Jka expression and the presence of anti-Jka, and guiding safe selection of antigen-negative blood.

Keywords

Kidd blood group system

Jka antigen

Jkb antigen

SLC14A1 gene

UT-B urea transporter

JK*01W weak Jka allele

anti-Jka antibody

delayed hemolytic transfusion reaction

molecular blood group genotyping

serologic discrepancy resolution