The low‐prevalence Rh antigen STEM (RH49) is encoded by two different RHCE*ce818T alleles that are often in cis to RHD*DOL

Abstract

BACKGROUND: STEM (RH49) is a low‐prevalence antigen in the Rh blood group system. A scarcity of anti‐STEM has precluded extensive study of this antigen. We report that two alleles with a RHCE*ce818C>T change encode a partial e, and a hrS−, hrB+, STEM+ phenotype and that both alleles are frequently in cis to RHD*DOL1 or RHD*DOL2. STUDY DESIGN AND METHODS: Blood samples were from donors and patients in our collections. Hemagglutination, DNA, and RNA testing was performed by standard techniques. RESULTS: Fourteen STEM+ samples were heterozygous RHCE*ce818C/T: six had RHCE*ceBI and eight had a novel allele, RHCE*ceSM. Eleven were heterozygous for RHD*DOL1 or RHD*DOL2. Eleven samples, previously typed STEM−, had RHCE*ce818C/C (consensus nucleotide). RBCs from informative STEM+ samples were e+/− hrS− hrB+. One person who was heterozygous RHCE*ceBI and RHCE*cE had an anti‐e‐like antibody in her plasma, and one person, who was hemizygous for RHD*DOL2, had anti‐D in her plasma. CONCLUSIONS: We show that two alleles with a RHCE*ce818C>T change (RHCE*ceBI and RHCE*ceSM) encode a hrS− hrB+ STEM+ phenotype. In addition, both alleles are frequently in cis to RHD*DOL1 or RHD*DOL2 and RHCE*ceBI encodes a partial e antigen. In the small cohort of samples tested, RHD*DOL invariably traveled with RHCE*ce818T. Our study also confirmed the presumption that RHD*DOL2, like RHD*DOL1, encodes a partial D antigen and the low‐prevalence antigen DAK.

The RHD*weak D type 4.0 allele is predominantly but not exclusively cis‐associated with the altered RHCE*ce(c.48C, c.105T, c.733G, c.744C, c.1025T) allele in the French population

“…latter haplotypes, which are both of clinical relevance (Faas et al, 1997;Daniels et al, 1998;Westhoff et al, 2001;Cotorruelo et al, 2007) and are compatible with those obtained with pattern 5 and possibly with pattern 6, segregates with the weak D type 4.0 allele. On the basis of our findings in these latter nine individuals and considering the weak D type 4.0 sample described by Reid et al (2013), one may speculate that some if not all samples might share haplotype RHD*weak D type 4.0/RHCE*ce(c.48C, c.733G), although this requires further molecular analyses. Conversely, no RHCE*ceCF allele, which was found to be cis-transmitted with a weak D type 4.0 allele in a single African-American female patient (Hipsky et al, 2011), could be found.…”

“…In an effort to characterise the haplotype of the weak D type 4.0 allele carriers in our population of interest, and to check whether other RHCE alleles segregate with this allele, as already described (Hipsky et al, 2011;Reid et al, 2013), we investigated the RHCE gene in donors carrying this variant D genotype in our laboratory. Sixty-nine different, consecutive samples referred to our laboratory by the local sites of the French Blood Center (Etablissement Français du Sang, France) from November 2009 to November 2012 and genotyped as weak D type 4.0 by direct sequencing (Le Maréchal et al, 2007;Fichou et al, 2013a) were selected for the study.…”

Effect on gene expression of three allelic variants in GATA motifs of ABO, RHD, and RHCE regulatory elements

“…Antigens c and e could not be used to determine the effect of 5′UTR‐83T on gene expression due to the presence of RHCE*ceJAL in trans. However, the low‐prevalence STEM antigen encoded by RHCE*ceSM offered an alternative. We found that an anti‐STEM serum agglutinated the donor RBCs with 4+ strength (Table ).…”

Rh and RHAG Blood Group Systems

“…Four RHCE genes (see Table 5.10 ), RHCE * ceAR , RHCE * ceEK , RHCE * ceBI , and RHCE * ceSM , encode Met238Val and weak e, but no hr S or Hr [338,340] , whereas RHCE * ceMO also produces weak e and no hr S or Hr, but encodes Val223Phe and not Met238Val [341] . Four RHCE genes (see Table 5.10 ), RHCE * ceAR , RHCE * ceEK , RHCE * ceBI , and RHCE * ceSM , encode Met238Val and weak e, but no hr S or Hr [338,340] , whereas RHCE * ceMO also produces weak e and no hr S or Hr, but encodes Val223Phe and not Met238Val [341] .…”