The Complexity of Human Leukocyte Antigen (HLA)-DQ Antibodies and Its Effect on Virtual Crossmatching

We previously reported that in patients possessing human leukocyte antigen (HLA)-DQ-directed antibodies, the target molecule may include the patient's own DQβ chain if it is paired with non-self-DQα chain, thus forming a different DQ target. Herein, we sought to assess the breadth of this phenomenon. Serum samples from 104 patients awaiting kidney transplantation, known to have DQ antibodies, were studied. Antibody identification was performed using luminex-based HLA class II single-antigen bead assays from two vendors; DQA1/DQB1 typing was performed using luminex polymerase chain reaction - sequence specific oligo prob hybridization (PCR-SSO) technology. A total of 71% of the 104 serum samples studied contained antibodies reactive against test beads coated with the patient's own DQα- or β-chain components. Of those, 35 patients (34%) exhibited antibodies to their own DQβ chain when in combination with non-self-DQα chains; and 64 patients (62%) had antibodies to their own DQα chain when in combination with non-self-DQβ chains. This is a striking observation. To the best of our knowledge, this is the first systematic, high-resolution evaluation of DQ antibody repertoire. With the expansion of virtual crossmatching, particularly in the context of a national registry, the need for more detailed DQ antibody or antigen evaluation is critical to improve operational efficiency and patient outcomes.