The role of HLA-DQ antibodies in decreasing solid organ graft outcome has recently been described. It is not clear, however, why HLA-DQ has different effects compared with other HLA class II antibodies, especially HLA-DR. We have sought to evaluate the nature of de-novo donor specific HLA-DQ antigen/antibody interactions.

The study population included only patients that had no HLA antibodies prior to their transplant (0%PRA), as detected by solid phase techniques, who following transplant rejected their organ and developed de-novo HLA-DQ DSA. Luminex-based single-antigen antibody testing was used to capture the complete make-up of HLA-DQ antibodies for individual patients. High resolution typing of donor and recipient HLA-DRB1, HLA-DQA1, and HLA-DQB1 was obtained either by molecular typing or use of most frequent HLA-DR-DQ linkage disequilibrium based on ethnic background. “HLA-Matchmaker” software was used to assess putative eplets (core of amino acid string recognized by the antibody), and Cn3D software was used to determine the specific location of the identified eplets within the HLA molecule’s structure as well as to assess the 15 Angstrom footprint of the antibody’s Complementarity Determining Regions (CDRs) – termed Functional Epitope.

Forty donor-recipient pairs were analyzed as described. In the vast majority of cases, all positive HLA-DQ responses were explainable by a single donor-specific eplet. In the other cases, more than one eplet was identified (those cases were excluded for the purpose of this study). More than 80% of the eplets identified were located in the HLA-DQ-beta chain. Importantly, regardless of the chain identified by HLA-Matchmaker to carry the relevant eplet, Cn3D software clearly demonstrated that the complete CDR footprint recognizing the antigenic target (15 Angstrom) included portions of both chains (alpha and beta) of the HLA-DQ molecule in >90% of cases analyzed.

We have recently published that listing donor HLA-DQ antigens as combinations of alpha-beta chains as well as listing the patients’ antibody specificities as such combinations increased highly sensitized patients’ access to transplantation at our center. The information reported here provides the likely explanation for this observation and suggests a need for a paradigm change in the way HLA-DQ antibodies are considered. We strongly encourage UNET to allow listing combinations of DQ alpha-beta as the patients’ unacceptable antigens as well as for the donor typing.

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