A comprehensive analysis of DEL types: partial DEL individuals are prone to anti‐D alloimmunization

Abstract

In conclusion, evidence is provided that different DEL genotypes code either for partial or complete D antigen expression and that this finding is clinically relevant.

Prospective Evaluation of a Transfusion Policy of RhD-Positive Red Blood Cells into DEL Patients in China

“…Amino acid substitutions in extracellular stretches of the D polypeptide lead to loss of one or more epDs, rendering also partial D individuals prone to anti-D alloimmunization upon contact with normal D+ RBCs expressing the complete set of epDs [14,15]. These reports support the possibility that a partial DEL phenotype could theoretically induce anti-D alloimmunization [9,11,14]. The antibody is also capable of causing severe hemolytic disease of the fetus and newborn (HDFN) in sensitized pregnant DEL women carrying an RhD+ fetus [9].…”

“…These reports support the possibility that a partial DEL phenotype could theoretically induce anti-D alloimmunization [9,11,14]. The antibody is also capable of causing severe hemolytic disease of the fetus and newborn (HDFN) in sensitized pregnant DEL women carrying an RhD+ fetus [9]. A partial D-like epitope loss has been reported in DEL phenotypes to be associated with the RHD (IVS3 + 1G>A) allele, and individuals with this phenotype can make anti-D [11].…”

“…Körmöczi and colleagues [9] proposed that DEL phenotypes should be divided into two subtypes: complete types where the majority of epDs are conserved such as RHD (1,227G>A) and partial D-like variants with characteristic epD loss caused by either RHD-CE-D hybrid genes or RHD point mutations RHD (IVS3 + 1G>A) affecting extracellular RhD loops. The distinction between complete and partial D is of clinical importance, because only partial D individuals exhibit a tendency to anti-D alloimmunization [9,11,14]. …”

“…The DEL phenotype arises from a mutation of the RHD gene, and more than 20 different DEL alleles have been described [4]. Molecular studies have indicated that DEL individuals retain a grossly intact D gene or a partial DEL with detectable D epitope (epD) loss [9,10,11,12,13]. D and CE polypeptides are coded for by the highly homologous RHD and RHCE genes.…”

Responder Individuality in Red Blood Cell Alloimmunization

“…Different RBC antigens feature characteristic antigen densities, varying widely from only a few to more than a million antigens per RBC [1]. For example, the highly immunogenic D antigen features an antigen density of 10,000-30,000 D sites per RBC, whereas different weak D variants and DEL types encompass the broad spectrum from a few thousand down to around 30 D sites per cell [25,26]. Even the weakest D variants were demonstrated to cause anti-D alloimmunization in D-negative individuals [27,28], but it seems that this happens rarely compared to challenge with normal D [29,30,31].…”