title: High frequency of partial DIIIa and DAR alleles found in sickle cell disease patients suggests increased risk of alloimmunization to RhD.
abstract: We have set out to determine the frequency of DIIIa and DAR alleles among sickle cell disease (SCD) patients. These D variants permit the unexpected development of antibodies to RhD among individuals who are otherwise classified as RhD+. DNA samples from 130 SCD patients were tested for 455A>C (specific for DIIIa), 602C>G, 667T>G (common for both DIIIa and DAR) and 1025T>C (specific for DAR) by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and sequence analysis. The PCR-RFLP showed that 12 (9.2%) of the SCD patients were carrying DIIIa and DAR alleles. Genomic DNA analysis performed by sequence showed that three samples were heterozygous DIIIa (2.3%), seven heterozygous DAR (4.6%) and two (1.5%) samples carried a partial D with four mutations: 455A>C (heterozygous), 602C>G and 667T>G (homozygous) and 1025T>C (heterozygous), indicating compound heterozygosity for one DIIIa allele and one DAR allele. The predicted phenotypes of eight (6.2%) SCD patients were DIIIa, DAR and DIIIa/DAR. Three patients were anti-D immunized (DAR, n = 1; DIIIa/DAR, n = 2). These findings suggest that SCD patients who are candidates for chronic transfusion may benefit from genotyping for DIIIa and DAR to prevent alloimmunization.
authors.affiliation: Hemocentro Unicamp, Campinas, SP, Brazil. castilho@unicamp.br
authors.forename: L
authors.initials: L
authors.lastname: Castilho
authors.forename: M
authors.initials: M
authors.lastname: Rios
authors.forename: A
authors.initials: A
authors.lastname: Rodrigues
authors.forename: J
authors.initials: J
authors.lastname: Pellegrino
authors.forename: S T O
authors.initials: ST
authors.lastname: Saad
authors.forename: F F
authors.initials: FF
authors.lastname: Costa
mesh_terms: D000483:Alleles; D000755:Anemia, Sickle Cell / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D001803:Blood Transfusion; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology; D005787:Gene Frequency / Q000276:immunology*; D006801:Humans; D007114:Immunization; D012204:Rh-Hr Blood-Group System / Q000235:genetics / Q000276:immunology*; D012307:Risk Factors; D065227:Transfusion Reaction
chemical_list: D012204:Rh-Hr Blood-Group System; C026410:Rho(D) antigen