The RHCE allele ceSL: the second example for D antigen expression without D-specific amino acids

Area of Science:

• Immunogenetics
• Blood group serology
• Molecular biology

Background:

• The RHce(R154T) allele (ceRT) demonstrated that D epitopes can be expressed without D-specific amino acids, leading to false-positive D antigen results in some ccddee blood donors.
• Previously, no other molecular mechanism for this phenomenon was identified.

Purpose of the Study:

• To identify and characterize novel molecular mechanisms responsible for false-positive D antigen expression in ccddee blood donors.
• To investigate the prevalence and genetic basis of such discrepancies in blood group typing.

Main Methods:

• Nucleotide sequencing of RHCE alleles from genomic DNA of ccddee individuals with false-positive anti-D reactions.
• Polymerase chain reaction with sequence-specific priming (PCR-SSP) for RHCE allele determination.
• Comparison of D epitope profiles with the known ceRT allele.
• Population frequency estimation through serology and molecular analysis in Switzerland and Germany.

Main Results:

• The RHCE allele RHce(S122L), designated ceSL, was identified as the cause of false-positive D antigen reactions in the cde haplotype.
• The ceSL phenotype expresses a limited number of D epitopes, specifically belonging to the D epitope 6 group.
• The frequency of ceSL among D-negative donors was approximately 1:675 in the Bern region of Switzerland, with no occurrences found elsewhere in Switzerland or southwestern Germany.

Conclusions:

• ceSL represents the second identified molecular mechanism for D antigen expression in the absence of D-specific amino acids.
• ceSL and ceRT elucidate the molecular basis of D antigen expression by RhCE proteins with non-representative amino acids.
• Significant variations in ceSL population frequencies were observed among Swiss and German populations.