BACKGROUND:  False-positive D typing in patients may lead to anti-D immunization caused by D+ transfusions or by omission of anti-D prophylaxis. Known causes of such errors are RhCE variants carrying RhD-specific amino acids and cold agglutinin activity of some frequently used monoclonal anti-D.

STUDY DESIGN AND METHODS:  The molecular basis of eight samples referred because of “false-positive” reactions with some commercial monoclonal anti-D was investigated by PCR and nucleotide sequencing from genomic DNA. PCR with sequence-specific priming was developed to specifically detect the underlying aberrant RHCE allele. The D epitope profile of the allele was determined by serology.

RESULTS:  The aberrant reactivity of the samples was caused by the RHCE allele RHCE(R154T) that occurred in a cde haplotype. The phenotype dubbed ceRT expressed the important D epitope 6, which is the target epitope of most monoclonal anti-D used in routine typing.

DISCUSSION:  The characterization of ceRT demonstrated a previously unknown mechanism of antigen D expression that does not require any D-specific amino acid. At least for some D epitopes, D-like structures may be mimicked by RhCE proteins carrying amino acid substitutions not representative for RhD.