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Abstract
An unusual HLA genotype association of DRB1∗07:01 and DQB1∗03:03 haplotype, expressing DRB4∗01, were identified in two Caucasian patients. The HLA phenotype of these patients showed the presence of DR53 with DR7 and DQ9 haplotype. The common null allele DRB4∗01:03N and the non-common associated DRB4∗01 were typed using serology (One Lambda), SSP Class II null tray and DR/DQ low and high resolution (One Lambda), SSO (One Lambda) and Real-Time PCR (Linkage). Typings were performed in parallel with other known patients to confirm these findings. The interpretation of all tests confirmed the DRB genotype to be DRB1∗07:01, DRB4∗01:01, DRB4∗03:01N. This unexpected expression of the DRB4∗01 with the DRB1∗07:01 and DQB1∗03:03 haplotype was seen only once before in a leukemia patient (Lardy et al., 1998). Sequencing studies are needed to collect more data and to determine the frequency of the linkage disequilibrium between the DRB1∗07:01 and DQB1∗03:03 haplotype expressing DRB4∗01. Serology typing played an important role determining these results because it indicated reflex testing to DNA typing was needed. Even though the DRB1∗07:01, DRB4∗01:03N and DQB1∗03:03 haplotype is common and the frequency is nearly 100%, the expression of the DRB4∗01 gene could be present when there is the DRB1∗07:01 and DQB1∗03:03 haplotype. Additional typing to determine the presence of DRB4∗01 should be considered in specific cases. For example, identifying this DRB4∗01 allele in organ donors is important to avoid the allocation of organs to patients with antibodies to DR53. Unexpected positive B-cell crossmatch in recipients with antibodies to DR53, when the donor has expressed DRB1∗07:01and DQB1∗03:03, should be investigated due to the possibility of the presence of DRB4∗01. Detecting this antigen on donors may be especially important for recipients with antibody to DR53, since expression of DR53 antigen on the donor may increase the possibility of antibody mediated rejection.Download : Download full-size image
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