A D+ blood donor with a novel RHD*D-CE(5-6)-D gene variant exhibits the low-frequency antigen RH23 (D(W) ) characteristic of the partial DVa phenotype.

Background: Blood donors whose red blood cells (RBCs) exhibit a partial RhD phenotype, lacking some D epitopes, present as D+ in routine screening. Such phenotypes can exhibit low-frequency antigens (LFAs) of clinical significance. The aim of this study was to describe the serologic and genetic profile for a blood donor with an apparent D+ phenotype carrying a variant RHD gene where D Exons 5 and 6 are replaced by RHCE Exon (5-6).

Study Design And Methods: Anti-D monoclonal antibodies were used to characterize the presentation of RhD epitopes on the RBCs. RHD exon scanning and DNA sequencing of short- and long-range polymerase chain reaction amplicons were used to determine the RHD structure and sequence. Extended phenotyping for LFAs RH23 (D(W) ) and Rh32 was performed.

Results: The donor serology profile was consistent with partial RhD epitope presentation. The donor was hemizygous for an RHD variant allele described as RHD*D-CE(5-6)-D hybrid. The RHCE gene insert is at least 3.868 kb with 5' and 3' breakpoints between IVS4 + 132-c.667 and IVS6 + 1960-IVS6 + 2099, respectively. The sequence for this hybrid was assigned GenBank Accession Number KT099190.2. The RBCs were RH23 (D(W) )+ and Rh32-.

Conclusion: A novel RHD*D-CE(5-6)-D hybrid allele encodes a partial RhD epitope and carries the LFA RH23 (D(W) ). This and the epitope profile resemble the partial DVa phenotype. Given that RBCs from this individual lack some RhD epitopes, there is an alloimmunization risk if the donor is exposed to D+ RBCs. Conversely, transfusions of RH23 (D(W) )+ cells to RH23 (D(W) )- recipients also pose an alloimmunization risk.