HLA ‐ DRB 1 *07:01 allele is primarily associated with the D iego a alloimmunization in a B razilian population

Background The D iego blood group presents a major polymorphic site at R esidue 854, causing a proline ( D i b antigen) to leucine ( D i a antigen) substitution. D i a alloimmunization has been observed among A sian and N ative S outh A merican populations. Considering that B razilians represent a genetically diverse population, and considering that we have observed a high incidence of D i a alloimmunization, we typed HLA ‐ DRB 1 alleles in these patients and performed in silico studies to investigate the possible associated mechanisms. Study Design and Methods We studied 212 alloimmunized patients, of whom 24 presented immunoglobulin G anti‐ D i a , 15 received D i(a+) red blood cells and were not immunized, and 1008 were healthy donors. HLA typing was performed using commercial kits. In silico analyses were performed using the TEPITOPE pan software to identify D iego‐derived anchor peptide binding to HLA ‐ DRB 1 molecules. Residue alignment was performed using the IMGT / HLA for amino acid identity and homology analyses. Results HLA ‐ DRB 1 * 07:01 allele was overrepresented in D i a ‐alloimmunized patients compared to nonimmunized patients and to healthy donors. Two motifs were predicted to be potential epitopes for D i a alloimmunization, the WVVKSTLAS motif was predicted to bind several HLA‐DR molecules, and the FVLILTVPL motif exhibited highest affinity for the HLA ‐ DRB 1*07:01 molecule. Pocket 4 of the DRB 1*07:01 molecule contained specific residues not found in other HLA ‐ DRB 1 molecules, particularly those at P ositions 13( Y ), 74( Q ), and 78( V ). Conclusion Individuals carrying the HLA ‐ DRB 1 * 07:01 allele present an increased risk for D i a alloimmunization. The identification of susceptible individuals and the knowledge of potential sensitization peptides are relevant approaches for transfusion care, diagnostic purposes, and desensitization therapies.