Identification of novel silent KEL alleles causing KEL:-5 (Ko) phenotype or discordance between KEL:1,-2 phenotype/KEL*01/02 genotype.

BACKGROUND: The Kell system, encoded by the KEL gene, is one of the most clinically important blood group systems. Molecular defects may lead to the absence of Kell antigen expression. The very rare KEL:5 results from silent KEL genes, also called KELnull alleles. In a few cases, the rare KEL:1,-2 phenotype may be associated with silent KEL*02 alleles. STUDY DESIGN AND METHODS: The aim of this study was to perform DNA investigations to identify silent KEL alleles among 10 KEL:-5 patients and 121 individuals presenting the rare KEL:1,-2 phenotype. Serologic investigations were performed on patients' red blood cells and serum. The KEL gene analysis was done by using a BeadChip assay (HEA Version, 1.2, Immucor), real-time polymerase chain reaction, and/or sequencing of all 19 exons of the KEL gene. RESULTS: In KEL:-5 patients, two novel KELnull alleles were described: 821G>A being the second described KELnull allele on a KEL*01 backbone and 184Tdel. In the 121 KEL:1,-2 individuals, nine (7.4%) were found to display a discordant KEL:1,-2 phenotype and KEL*01/KEL*02 genotype. Three novel silent KEL*02 alleles were described: 1084C>A, 1708G>A, and IVS11+5g>a. CONCLUSION: The number of silent KEL alleles and the notion that KEL null alleles are on a KEL*02 background may evolve in the coming years. Systematic DNA analysis showed that the number of discordant phenotype/genotype results, related to silent KEL*02 alleles was higher than expected in France. These data emphasize that clinical practice based on DNA analysis for blood group antigens requires caution and should improve the performance of the blood group phenotype prediction.

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).