PubMed · 805503
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H F Sandmire. 1975. The Rh factor.. https://pubmed.ncbi.nlm.nih.gov/805503/
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While the previous review encompassed the Rh blood group system (Chou ST, Westhoff CM. The Rh and RhAG blood group systems. Immunohematology. 2010;26:178-86), this update focusses on the RHCE gene and its variants. Four new antigens- PARG, CEVF, CEWA, and CETW (RH60 to RH63)-were reported since the last update. RHCE*cEMI (RHCE*03.31) was amended from a null allele to an allele encoding very weak antigen expression. The following topics are discussed: cross-reactive alleles [such as RHCE*ceHAR (*01.22.01) and RHCE*ceCF (*01.20.06) which may type D+ with some monoclonal anti-D reagents], issues with hybrid alleles and allele dropout, common haplotypes (association between RHCE alleles and specific RHD alleles), and clinical considerations. While the detailed description of new Rh antigens has become rare, many RHCE alleles have been reported since the previous review, a result of increased adoption of DNAbased testing for red blood cell antigens in immunohematology laboratories. The Rh blood group system has fascinated generations of immunohematologists and is likely to continue to do so for decades to come.
BACKGROUND: Patients with chronic transfusion needs such as those with sickle cell disease face a high risk of developing antibodies against high-prevalence antigens in the RH blood group system, complicating transfusion therapy and potentially necessitating stem cell transplantation. Molecular characterization of the RH system is hindered by hybrid alleles and high sequence homology between RHD and RHCE, limiting the effectiveness of conventional short-read sequencing. STUDY DESIGN AND METHODS: We analyzed 11 control and 20 patient samples, some of which could not be reliably genotyped by standard methods. RESULTS: Nanopore sequencing with adaptive sampling enables targeted, amplification-free long-read sequencing of the RH locus, resolving homologous and complex hybrid structures and enabling complete haplotype phasing for all samples, including samples that could not be accurately determined by standard methods like serology and short-read sequencing. Four new alleles were identified and for 13 out of 20 patients the results led to a change in the transfusion regimen. DISCUSSION: These findings show that nanopore sequencing with adaptive sampling allows unambiguous genotyping of the RH system, improves detection of complex variants, and supports better-matched transfusion strategies for chronically transfused patients.
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