High frequency of partial DIIIa and DAR alleles found in sickle cell disease patients suggests increased risk of alloimmunization to RhD

Author(s)

Castilho, L. ; Rios, M. ; Rodrigues, A. ; Pellegrino Júnior, J. ; Saad, S. T. O. ; Costa, F. F. ^[6]

• Document type: Journal article
• Source: Transfusion Medicine; v. 15, n. 1, p. 49-55, Feb. 2005.
• Field of knowledge: Health Sciences - Medicine

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. (AU)

• FAPESP's process: 02/13801-7 - Hereditary hemoglobin disorders: molecular genetics, clinical features and animal models with the production of transgenic animals
• Grantee: Fernando Ferreira Costa
• Support Opportunities: Research Projects - Thematic Grants