MOLECULAR BASIS DETERMINATION OF D VARIANTS: NARRATIVE REVIEW

Abstract

Objective: The Rh blood group is one of the most complex blood groups known in humans, being is clinically relevant mainly due to the fact that antigens are highly immunogenic, responsible for a hemolytic transfusion reaction or on fetal RBCs. The RH system (ISBT004) is the most complex, polymorphic and immunogenic of the blood groups due to the presence of 55 antigens carried by the RhD and RhCE proteins, encoded by two homologous genes, RHD and RHCE, located on chromosome 1. The proximity and opposite orientation of these genes allow the occurrence in a hybrid gene, with several variant phenotypes and possibility of generating alloimmunization. The RHD gene, consisting of 10 exons, has 57295pb and encodes a polypeptide of 417 amino acids. The objective of this study was to conduct a reviewer of the main molecular aspects of the D antigen. Materials and methods: This is a narrative review study, using the Pubmed and Web of Science databases, without a specific time period determined. The descriptors and their synonyms “Rh-Hr Blood-Group System”, “Blood Donors”, “Patients”and “Gene Frequency”were used, associated with each other using the Boolean operators AND/OR. Results: A total of 285 articles were found, of which only 52 were selected after reading the abstract and then reading them in full. Duplicate articles or those that did not specifically address the topic to be discussed were excluded. Discussion: Mutations and polymorphisms in the RHD gene can result in structural alterations of the D protein, producing variant D phenotypes: the weak D phenotype results from a single point mutation with reduced antigenicity and a rare risk of alloimmunization, with the exception of weak D types 6, 7, 11, 15, and 4.2 (DAR); the partial D phenotype has immunogenic D epitopes and a tendency to develop Anti-D; the DEL phenotype, occurs in 10 to 33% of Japanese and Chinese people, commonly referred to as DEL “Asian-type”, and is only identified on the red cell membrane after adsorption with anti-D followed by elution. The distribution of D alleles varies considerably among ethnicities, and regional data is needed to implement an efficient genotyping strategy to prevent alloimmunization and minimize problems related to discordant D serological typing results. Conclusion: Studies involving molecular techniques of the Rh system allowed the expansion of better and advanced techniques in the determination of variants in different populations. The molecular genetics of RHD and the global distribution of RH variants in Caucasians, Black Africans, and East Asians are now well established. Determining these variant phenotypes through genetic and molecular studies is important in guiding transfusion practices and the administration of Anti-D prophylaxis to avoid complications and reactions after transfusions. Added to this, in the field of obstetrics, it has been increasingly helping in the phenotypic, genotypic correlation and Rh alloimmunization, especially avoiding inappropriate anti-D immunoprophylaxis with the specific weak D type.