RHCE*ceMO is frequently in cis to RHD*DAU0 and encodes a hr^S–, hr^B–, RH:–61 phenotype in black persons: clinical significance

Abstract

Background RHCE*ceMO has nucleotide changes 48G>C and 667G>T, which encode, respectively, 16Cys and 223Phe associated with altered expression of e antigen. RHD*DAU0 has nt1136C>T, which encodes 379Met associated with normal levels of D. We compiled serologic and DNA testing data on samples with RHCE*ceMO to determine the RBC antigen expression, antibody specificity, RHD association, and the prevalence in African-Americans. Methods Serologic testing was performed by standard methods. Genomic DNA was used for PCR-RFLP and RH- exon sequencing, and for some, Rh-cDNA was sequenced. Seventy-seven (50 donor and 27 patient) samples with RHCE*ceMO were studied, and 350 African-Americans were screened for allele prevalence. Results RBCs from RHCE*ceMO homozygotes (or heterozygotes with RHCE*cE in trans) were weakly or non-reactive with some anti-e , and were non-reactive with polyclonal anti-hrS and anti-hrB. Twenty-three transfused patients homozygous for RHCE*ceMO/ceMO or with RHCE*ceMO in trans to RHCE*cE or *ce had allo anti-e, anti-f, anti-hrS/hrB, or an antibody to a high prevalence Rh antigen. Three patients with allo-anti-c had RHCE*ceMO in trans to RHCE*Ce. RHD*DAU0 was present in 30% of African-Americans tested and in 69 of 77 (90%) of samples with RHCE*ceMO. Conclusions RHCE*ceMO encodes partial e, as previously reported, and also encodes partial c, a hrS– and hrB– phenotype, and the absence of a high prevalence antigen (RH61). The antibody in transfused patients depended on the RHCE allele in trans. RHCE*ceMO was present in 1 in 50 African-Americans with an allele frequency of 0.01, is often linked to RHD*DAU0, and is potentially of clinical significance for transfusion.

Comprehensive red blood cell and platelet antigen prediction from whole genome sequencing: proof of principle

“…Relative to the conventional reference sequence for RHD (L08429) the human reference genome is c.1136C>T (chr1:25,643,553C>T) p.Thr379Met, which corresponds to the family of DAU alleles, specifically RHD*DAU0, which is primarily found in African Americans . The conventional reference sequence (DQ322275) for RHCE*ce ( RHCE*01) encodes a c+e+ phenotype . The human reference genome RHCE sequence is c.48G>C, chr1:25,747,230G>C (p.Trp16Cys), which corresponds to RHCE*ce(48C) ( RHCE*01.01), again, an allele more often found in African Americans.…”

“…(RHCE*01) encodes a c1e1 phenotype [46][47][48]. The human reference genome RHCE sequence is c.48G>C, chr1:25,747,230G>C (p.Trp16Cys),…”

Molecular matching for patients with haematological diseases expressing altered RHD‐RHCE genotypes

“…Thus, patients with African descent can produce complex Rh alloantibody(ies), making to find compatible blood a challenge [11,12]. Furthermore, the variant RHCE can be inherited in cis with an altered RHD [13][14][15][16][17].…”

Genotyping in Sickle Cell Disease Patients: The French Strategy

“…Many partial antigens and rare blood types have been described in the RH system [1,3,4,5], including several found in patients in France [6,7]. RH variants are considered relevant in SCD patients [8], due to the risk of allo-antibody formation.…”