Molecular and serologic characterization of DWI, a novel "high-grade" partial D.
BACKGROUND
Accurate D antigen identification is essential for pretransfusion and prenatal evaluation to prevent anti-D alloimmunization. Quantitative and qualitative D variants may pose typing problems and require particular consideration because of differing potential for anti-D induction.


METHODS
A novel partial D, DWI, was discovered in an anti-D-alloimmunized D+ Austrian woman. This D variant was investigated by RHD genotyping and nucleotide sequencing, as well as characterization of its serologic properties.


RESULTS
The proposita exhibited a single-nucleotide exchange in RHD Exon 7 (1073T>C) predicting a Met358Thr substitution in the sixth extracellular loop of the RhD polypeptide. All DWI individuals identified (the proposita and two relatives) were genotyped DWIdCcee, which, together with the family tree, was highly suggestive of a DWICe haplotype association. Epitope mapping studies revealed only minor D antigen modification with weakening but not loss of epitopes D1.1, D9.1, and D16.1. Antigen density varied individually between 8000 and 8600 D sites per erythrocyte. No known low-frequency Rh antigen was detected. Despite the highly retained D epitope composition, the DWI proposita's serum sample contained alloanti-D from an immunization event many years earlier.


CONCLUSIONS
The findings of this investigation emphasize the possible clinical significance of "high-grade" partial D variants that are likely to be missed by routine serology.
Körmöczi
Günther F
GF
Department of Blood Group Serology, University of Vienna, Austria. guenther.koermoeczi@meduniwien.ac.at
Legler
Tobias J
TJ
Daniels
Geoff L
GL
Green
Caroll A
CA
Struckmann
Renate
R
Jungbauer
Christof
C
Moser
Sabine
S
Flexer
Manuela
M
Schönitzer
Diether
D
Panzer
Simon
S
Gassner
Christoph
C
D000368:Aged; D019943:Amino Acid Substitution; D000915:Antibody Affinity; D018604:Epitope Mapping; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007518:Isoantibodies / Q000097:blood; D020641:Polymorphism, Single Nucleotide; D012203:Rh Isoimmunization; D012204:Rh-Hr Blood-Group System / Q000097:blood / Q000235:genetics* / Q000276:immunology; D018029:Rho(D) Immune Globulin
D007518:Isoantibodies; C061961:RHO(D) antibody; D012204:Rh-Hr Blood-Group System; D018029:Rho(D) Immune Globulin; C026410:Rho(D) antigen