A novel KEL*1,3 allele with weak Kell antigen expression  confirming the cis-modifier effect of KEL3.
BACKGROUND
KEL1 (K) is the most immunogenic red blood cell antigen of the Kell blood group system. The frequently occurring anti-KEL1 alloantibodies may cause hemolytic transfusion reactions as well as severe hemolytic disease of the fetus and newborn. So far, reports on weak KEL phenotypes are scarce.


METHODS
Blood samples of two unrelated Central European propositi with faint reactions in routine KEL1 typing were analyzed by extended serologic phenotyping, flow cytometry, genotyping by polymerase chain reaction with sequence-specific priming, and genomic DNA sequencing of separated parental KEL alleles.


RESULTS
Both propositi exhibited an unusual KEL:1,2,3,4 phenotype: markedly weakened and negative reactions were observed in serologic KEL1 typing in gel and tube technique, respectively. No KEL1 epitope loss was detected using five different monoclonal anti-KEL1 reagents. KEL genotyping confirmed KEL*1/2 and KEL*3/4 (Kpa/Kpb) heterozygosity of both individuals. Importantly, DNA sequencing of the two separated parental alleles of both propositi revealed a KEL*1-specific coding nucleotide T578 and a KEL*3-specific T841 on the same allele. This novel KEL*1,3 (KKpa)allele was associated with an approximately 80 percent reduction in KEL1 expression, compared to KEL:1,2,-3,4 controls. The low KEL1 density was attributed to acis-modifier effect of KEL3, so far only reported in association with weakened expression of KEL2 (k).


CONCLUSIONS
This is the first description of the KEL*1,3 allele encoding KEL1 and KEL3 on the same molecule. In individuals with weakened KEL1 because of KEL3 in cis, very sensitive serologic or molecular genetic techniques may be required for reliable Kell typing.
Körmöczi
Günther F
GF
Department of Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Währinger Gürtel 18-20, Vienna, Austria. guenther.koermoeczi@meduniwien.ac.at
Scharberg
Erwin A
EA
Gassner
Christoph
C
D000483:Alleles; D004252:DNA Mutational Analysis; D004912:Erythrocytes / Q000166:cytology / Q000378:metabolism; D005434:Flow Cytometry; D015870:Gene Expression; D005787:Gene Frequency; D005838:Genotype; D006650:Histocompatibility Testing; D006801:Humans; D016130:Immunophenotyping; D007626:Kell Blood-Group System / Q000235:genetics* / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid / Q000502:physiology*
D007626:Kell Blood-Group System; D020033:Protein Isoforms