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The Cutting Edge of HLA Diagnostics.

S ince the 1950s, landmark twin transplant studies at the Peter Bent Brigham Hospital in Boston, Massachusetts, the critical role of histocompatibility has been evident. Nevertheless, 2 pivotal advances in the 1960s were required tomake transplantation across HLA barriers available to all patients with end-stage organ failure: (1) the identification of effective immunosuppressive combinations; and (2) the development of a diagnostic assay to detect preexisting recipient humoral memory to the donor, which if crossed, would lead to hyperacute allograft rejection. Thereafter, the transplant community has seen continuous advances in both of these fields of study that have directly impacted patients by improving outcomes. While advances were made between the 1960s and 1990s in HLA diagnostics, it was not until the advent of molecular biology technologies that the field of histocompatibility underwent a modern renaissance. Indeed, solid-phase microbeads, coated with purified HLA proteins, have allowed for novel mechanistic insights into the role donor-specific HLA antibodies (DSA) play in limiting allograft survival both pretransplant and posttransplant and refocused the attention of the community on the humoral arm of the alloimmune response. Characterization of antibody features that are critical for effector functions may help to identify HLA antibodies that are more likely to cause rejection. Several recent modifications proposed to these solid-phase assays explore whether the attributes of donor specificHLA antibodies hold diagnostic or prognostic utility in patient care. It is in this context that the current supplement has been conceived. Liwski and Gebel provide a comprehensive overview of the evolution in HLA diagnostics. They lay out the strengths, limitations and pitfalls of both cell-based and solid phase assays. Further, they highlight key considerations when interpreting HLA diagnostics and their requirement to be integrated with the clinical context. Most importantly, they emphasize the critical requirement to have excellent communication between the laboratory and the clinical teams.