HLA-DQ antibodies: are they real? Are they relevant? Why so many?

Abstract

Recent reports on donor-specific antibodies documented an overwhelming frequency of antibodies to one specific locus – human leukocyte antigen DQ (HLA-DQ). This article provides a short summary of clinical observations, a historic perspective to account for the late recognition of the role of HLA-DQ antibodies as well as potential explanations.

The basic understanding of the complexity of HLA-DQ molecules (antigens and antibodies) existed already 3–4 decades ago. However, only more recent advancements in molecular techniques as well as solid phase platforms, that allow for testing antibody specificities against individual HLA targets, provided state-of-the-art tools that are also amenable to mass applications. Thus, the significance of the polymorphic nature of both polypeptide chains of the DQ molecule, DQα and DQβ, is only now re-emerging.

HLA-DQ antibodies are real, relevant, and abundant. In order to achieve a clinically useful understanding of this phenomenon, HLA-DQ antigens and antibodies should be viewed at the level of the physiologic structure, as it appears on the cell surface, namely, one unit composed as DQαβ. Preliminary data demonstrated that such an approach is likely to lead to more equitable calculation of calculated panel reactive antibody, improving the accuracy of virtual crossmatch prediction, and increasing the likelihood of finding a compatible donor for the very highly sensitized patients.