HLA-DQB1∗03:25: A rare allele with a serological equivalency of HLA-DQ4

Abstract

Aim HLA-DBQ1∗03:25, a rare allele of Hispanic origin identified in 2008, has not yet been assigned a serological equivalent. A recent observation in our center of a 75 year old Hispanic female patient typed as DQB1∗03:25 who also displayed HLA-DQ7, -DQ8 and -DQ9 antibodies triggered an investigation of the serological equivalency for this allele. Methods Molecular HLA typing was performed by LabType SSO (One Lambda), LinkSeq Real-Time PCR HLA typing (Linkage BioSciences) and LIFECODES HLA SSO Typing (Immucor). Serological HLA typing was performed by Lambda Monoclonal Trays (LMT) HLA class II typing tray (One Lambda). Antibody analysis was performed by LABScreen Single Antigen HLA class I and class II kits (One Lambda) and LIFECODES class I and class II ID kits (Immucor). Results The patient was initially typed by LabType SSO as HLA-A∗02, 03; B∗39, 44; C∗04, 07; DRB1∗07, 09; DQB1∗02:02, 03:25. Further DNA typing by real-time PCR SSP confirmed the same results. DQB1 typing further confirmed by LIFECODES SSO typing. Since the patient presented HLA-DQ7, -DQ8 and -DQ9 antibodies, serological HLA class II typing was subsequently performed yielding the following. Results DR7, 9; DQ2, 4. DNA and protein sequence alignments of the DQB1∗03:25 allele with other DQB1 alleles showed that its sequence is quite similar with the DQB1∗04:03 allele, but differs significantly from the DQB1∗03 alleles. The sequence difference between DQB1∗03:25 and DQB1∗04:03 is only one amino acid at codon 9 in exon 2 (Tyr vs. Phe). Thus, DQB1∗03:25 shows almost identical immunogenicity to DQB1∗04:03 in the context of their sequences. When compared with the first case of HLA-DQB1∗03:25 in IMGT/HLA database, it was noticed that both cases carry the DRB1∗09-DQB1∗03:25 haplotype. Conclusion This is the first time to confirm that the serological equivalent of DQB1∗03:25 is DQ4. In this regard, accurate antigenic entry of deceased donor HLA typing into UNET is critical since it affects multiple areas of organ allocation, particularly given the increased utilization of virtual crossmatching to determine the compatibility of a potential donor prior to organ allocation. In addition, based on our knowledge, this is the second case of the DQB1∗03:25 allele in the Hispanic population. It suggests an expanded population study needed to document this allele well.