Two Alleles with RHCE*nt818C>T Change Encode the Low Prevalence Rh Antigen STEM.

According to the original (and only) report, the low prevalence Rh antigen, STEM, is associated with an altered e phenotype. Approximately 65% of hr^S– and 30% of hr^B– RBCs from South African donors are STEM+. STEM has a variable expression, which is an inherited characteristic. Anti-STEM has induced mild HDFN (Marais, et al., Transf Med 1993;3:35-41). The purpose of this study was to determine the molecular basis associated with STEM expression.

Blood samples and reagents were from our collections. Hemagglutination and DNA extraction were performed by standard methods. Molecular testing included direct sequencing and cloning of cDNA, AS-PCR, PCR-FRLP, and sequencing specific exons of gDNA.

Three STEM+ samples (including the original index case) had RHCE*ceBI [ce 48C (16C), 712G (238V), 818T (273V), 1132G (378V)] (Noizat-Pirenne, et al., Blood 2002;100:4223-31) and 6 had a new allele, which we name RHCE*ceSM (ce 48C, 712G, 818T). In contrast, 8 STEM– samples (which included hr^S– and hr^B– samples) did not have the RHCE*818C>T change. RBCs with the ceBI phenotype expressed STEM more strongly than those with the ceSM phenotype.

The previously reported allele RHCE*ceBI and a new allele, RHCE*ceSM, encode the STEM antigen. This study also revealed other new findings: (i) ceSM encodes a weaker expression of STEM than does ceBI, which explains the previously reported variable expression, (ii) provides an explanation for why not all hr^S– and hr^B– RBCs express STEM. RBCs with ceAR, ceMO, and ceEK, phenotypes are hr^S– STEM–, and RBCs with ce^S phenotypes type hr^B–, STEM–, (iii) ceBI and ceSM do not express hr^S but do express hr^B. It is likely that anti-hr^S made by hr^S– STEM– people (ceAR, ceMO, ceEK) will be incompatible with hr^S– STEM+ RBCs, and vice versa. Our findings provide a means to positively identify the STEM+ phenotypes, which, by hemagglutination, is virtually impossible due to the dearth of anti-STEM. Further, it provides a tool to provide suitable antigen-negative RBC products to a patient who has made an ‘e-like’ antibody.

No relevant conflicts of interest to declare.