The RHCE allele ceRT: D epitope 6 expression does not require D‐specific amino acids

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Abstract
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.