title: Characterization of Jk(a+(weak)): a new blood group phenotype associated with an altered JK*01 allele.
abstract: BACKGROUND
  The clinically important Kidd (JK) blood group system is considered to be relatively uncomplicated, both serologically and genetically. The JK*01 and JK*02 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.
  
  
  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 JK*01 allele carrying 130G>A (Glu44Lys) and the JK*02-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.
authors.affiliation: Division of Hematology and Transfusion Medicine, Department of Laboratory Medicine, Lund University, Lund, Sweden.
authors.forename: Elisabet S
authors.initials: ES
authors.lastname: Wester
authors.forename: Jill R
authors.initials: JR
authors.lastname: Storry
authors.forename: Martin L
authors.initials: ML
authors.lastname: Olsson
mesh_terms: D000483:Alleles; D019943:Amino Acid Substitution; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D001788:Blood Grouping and Crossmatching; D015153:Blotting, Western; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006461:Hemolysis; D006801:Humans; D007667:Kidd Blood-Group System / Q000235:genetics*; D008297:Male; D026901:Membrane Transport Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D010641:Phenotype; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D017422:Sequence Analysis, DNA; D014158:Transcription, Genetic; D000096982:Urea Transporters
chemical_list: D000888:Antibodies, Anti-Idiotypic; D007667:Kidd Blood-Group System; D026901:Membrane Transport Proteins; D012333:RNA, Messenger; D000096982:Urea Transporters