RHD*DOL1 and RHD*DOL2 encode a partial D antigen and are in cis with the rare RHCE*ceBI allele in people of African descent.

BACKGROUND: Several studies showed in people of African descent the existence of a genetic linkage between RHD alleles encoding a variant D antigen and a given altered RHCE*ce allele. RHCE*ceBI is a rare allele encountered in people of African descent, that encodes a Hr- hr(S) - Rhce protein. Our study shows that RHCE*ceBI appears to be genetically linked to two very similar variant RHD alleles, RHD*DOL1 and RHD*DOL2, and demonstrates for the first time that DOL-2 is a partial D antigen. STUDY DESIGN AND METHODS: After finding out an individual with both RHCE*ceBI and RHD*DOL presumed to be in cis, we hypothesized a genetic linkage between those two genes. All individuals (n = 7) known to carry RHCE*ceBI in our laboratory, including the index case, were fully investigated at the serologic and molecular level. RESULTS: One individual with alloanti-D, being homozygous for RHCE*ceBI and RHD*DOL2, allowed us to confirm the genetic linkage between those two genes, as well as the partial D status of DOL-2. In the six RHCE*ceBI remaining individuals, three were found with RHD*DOL2 and 3 with RHD*DOL1, likely in cis. Three of them made an alloanti-D; one was DOL-1 and two were DOL-2. CONCLUSION: The rare RHCE*ceBI allele appears to be in cis either with RHD*DOL1 or with RHD*DOL2 in people of African descent. DOL-1 and DOL-2 must be considered as partial D antigens. We recommend a systematic search for RHD*DOL1 and RHD*DOL2 in people found to carry RHCE*ceBI and vice versa, especially in patients with sickle cell disease.

Analysis of RhCE variants among 806 individuals in France: considerations for transfusion safety, with emphasis on patients with sickle cell disease.

BACKGROUND: DNA testing has enabled the documenting of numerous variants of RHCE alleles, especially in individuals of African origin. The risk for production of clinically significant alloantibodies to Rh antigens of patients carrying variant RHCE alleles has led us to analyze the different RhCE variants investigated by molecular biology. Alloimmunization was analyzed regarding the RHCE genetic profile. STUDY DESIGN AND METHODS: Samples from 806 individuals with altered expression of RhCE antigens and/or producing anti-RhCE in the presence of the corresponding antigen were analyzed. RESULTS: A total of 572 individuals were shown to express RhCE variants. Variant RHCE*ce alleles and RH haplotypes were identified in 83% of cases, the most frequent ones being the R(N) haplotype, the ceMO allele, the (C)ce(s) haplotype/ce(s) 1006 allele, and the ceAR allele identified in 36, 23, 20, and 17% of the tested samples, respectively. The absence of a high-prevalence Rh antigen was documented in 93 individuals. Partial C and partial e were expressed by 53% of individuals with RhCE variants. Rh antibodies were identified in 127 (20%) of 623 patients. They were found to be alloantibodies in 48 (38%) of these 127 patients. Alloimmunization against a high-prevalence Rh antigen was detected in 25% of cases. CONCLUSION: The challenge in clinical red blood cell (RBC) transfusion of patients with sickle cell disease, notably, would be to provide not only phenotypically matched, but also genetically matched, RBC units regarding RhCE variants.

Alloanti-c/ce in a c+ceAR/Ce patient suggests that the rare RHCE ceAR allele (ceAR) encodes a partial c antigen.

BACKGROUND: ceAR (RHCE ceAR) is a rare RH allele encountered in people of African/Caribbean ancestry, known to encode a partial e antigen. The homozygous ceAR/ceAR genotype encodes the rare blood group Hr-. This study describes alloanti-c/ce in a ceAR/Ce patient, suggesting that ceAR also encodes a partial c antigen. CASE REPORT: A 21-year-old patient suffering from intermediate beta-thalassemia, with transfusion history, was hospitalized for severe anemia. Blood samples were referred to the National Reference Laboratory for suspicion of a mixture of alloantibodies or an alloantibody to a high-prevalence antigen. MATERIALS AND METHODS: Standard hemagglutination methods were performed to investigate the patient's RBCs and serum. A molecular analysis of RHD and RHCE was carried out by allele-specific polymerase chain reaction and DNA sequencing. RESULTS: Blood type performed by the referring laboratory was B, D+C+E-c+e+, K-. Several antibodies were identified: anti-c/ce, anti-Fy(b), anti-Jk(a), and anti-S. Full serologic investigations showed that anti-c/ce could be very likely considered as an alloantibody. The patient's genotype was ceAR/Ce. Anti-c/ce reacted with ceAR/ceEK, ceEK/ceEK, and ceAR/ceBI but not with ceAR/ceAR, ceMO/ceMO, and ce(s)(340)/ce(s)(340) RBCs. CONCLUSION: This is the first case of alloanti-c/ce related to ceAR, suggesting that this rare RHCE allele encodes a partial c antigen. The presence of the C antigen in the patient allowed for the partial expression of the c antigen encoded by ceAR. The c antigen encoded by ceAR appeared to be different than that encoded by ceEK and ceBI and may share common lacking epitopes with the c antigens encoded by ceMO and ce(s)(340).