The DAU allele cluster of the RHDgene

Wagner, Franz F.; Ladewig, Birgit; Angert, Katharina S.; Heymann, Guido A.; Eicher, Nicole I.; Flegel, Willy A.

doi:10.1182/blood-2002-01-0320

Cited by 83 publications

(149 citation statements)

References 40 publications

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“…Sixty-six percent had an RHD pseudogene (RHD) that contains a 37-bp insertion that results in a premature stop codon, 15% had a DIIIa-CE(4-7)-D hybrid gene characterized by C-antigen expression but no D, and only 18% had deletion of the entire RHD gene. 45 Of 320 African-American patients with SCD, 16 phenotyped D Ϫ , of which 12 were homozygous for RHD gene deletion, 2 were homozygous RHD, and 2 were heterozygous for the gene deletion 39,47 In our cohort of 320 patients, 49% of D ϩ patients had conventional RHD only, 30% had at least one variant and one conventional RHD, and 21% had only variant RHD alleles (either homozygous or compound heterozygous; Table 1). Of the individuals with only variant RHD alleles, 71% had 1 or 2 DAU0 alleles, which has a similarly high frequency in African-American donors.…”

Section: Variations In Rhdmentioning

confidence: 99%

Transfusion therapy for sickle cell disease: a balancing act

Chou

2013

Hematology

108

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Transfusion therapy is a key intervention in decreasing morbidity and mortality in patients with sickle cell disease (SCD). Current indications for acute and chronic transfusion therapy have significantly increased the number of RBC units transfused to patients with SCD worldwide. This review summarizes transfusion management for the treatment or prevention of neurologic and perioperative complications, acute chest syndrome, and acute anemia associated with SCD. Despite the recognized benefits of transfusion therapy, it is not without the risks of iron overload, alloimmunization, and delayed hemolytic transfusion reactions. Transfusional iron overload management includes automated RBC exchange, noninvasive imaging to monitor iron burden, and iron chelation with parenteral or oral agents. Although limited and extended RBC antigen matching reduces antibody formation, the prevalence of RBC alloimmunization in patients with SCD remains high. Recent studies demonstrate that RH genetic diversity in patients with SCD contributes to Rh alloimmunization, suggesting that even more refined RBC matching strategies are needed. Advances in molecular blood group typing offer new opportunities to improve RBC matching of donors and recipients and can be of particular benefit to patients with SCD.

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Section: Variations In Rhdmentioning

confidence: 99%

Transfusion therapy for sickle cell disease: a balancing act

Chou

2013

Hematology

108

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“…For example, RHD encodes the D antigen ("Rh positive"), but individuals with altered RHD encoding partial D, defined as missing some D epitopes, may form anti-D when exposed to conventional D antigen. [23][24][25][26] In contrast, individuals with altered RHD encoding weak D, defined as expressing a reduced amount of D antigen but not lacking epitopes, are not typically at risk for anti-D. 20,27 Variant RHCE alleles are also prevalent in individuals of African descent, with alleles encoding partial e antigen most often encountered.…”

Section: Introductionmentioning

confidence: 99%

High prevalence of red blood cell alloimmunization in sickle cell disease despite transfusion from Rh-matched minority donors

Chou

Jackson

Vege

et al. 2013

Blood

397

492

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• Rh serologic phenotype-matched transfusions from minority donors do not prevent all Rh alloimmunization in patients with SCD.• Variant RH genes are common in patients with SCD and contribute to Rh alloimmunization and transfusion reactions.Red blood cell (RBC) transfusion is a key treatment of patients with sickle cell disease (SCD) but remains complicated by RBC immunization. In the present study, we evaluated the effects of antigen matching for Rh D, C, and E, and K and transfusion from African American donors in 182 patients with SCD. Overall, 71 (58%) chronic and 9 (15%) episodically transfused patients were alloimmunized. Fifty-five (45%) chronic and 7 (12%) episodically transfused patients were Rh immunized. Of 146 antibodies identified, 91 were unexplained Rh antibodies, one-third of which were associated with laboratory evidence of delayed transfusion reactions. Fifty-six antibodies occurred in patients whose RBCs were phenotypically positive for the corresponding Rh antigen and 35 in patients whose RBCs lacked the antigen and were transfused with Rh-matched RBCs. High-resolution RH genotyping revealed variant alleles in 87% of individuals. These data describe the prevalence of Rh alloimmunization in patients with SCD transfused with phenotypic Rh-matched African American RBCs. Our results suggest that altered RH alleles in both the patients and in the donors contributed to Rh alloimmunization in this study. Whether RH genotyping of patients and minority donors will reduce Rh alloimmunization in SCD needs to be examined. (Blood. 2013;122 (6):1062-1071

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“…Hemker et al studied 326 individuals from South Africa and reported a frequency of 4.9% for the DAR allele, representing 1.5% of all homozygotes or hemizygotes [15]. In populations of Caucasian origin, however, the frequency of the DAR allele is lower than in populations of African origin, with reported frequencies lower than 0.1% [10]. The frequency of the DAR allele reported by Avent in 2009 was 0.0002%, while the frequency of the DAU allele was 0.0001% among 33,864 healthy individuals from a German population.…”

Section: Discussionmentioning

confidence: 99%

“…In Brazil, the DAU allele has not been reported previously, and the high frequency of this allele among our SCD patients demonstrates the relevance of this work. In our study, the variant DAU was identified by a single codon mutation, 1136C>T [10]. Thus, the DAU allele, compared with DIIIa and DAR, was the most frequent in the SCD patients studied.…”

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confidence: 94%