Technical aspects of HLA antibody testing

Since the landmark studies of Patel and Terasaki, pretransplant identification of donor-directed HLA alloantibodies (DSAs) has been a critical prelude to renal allograft transplantation. Pretransplant, DSAs may be an acceptable risk or an unconditional contraindication to transplantation depending on the particular donor : recipient combination. Posttransplant, DSAs are associated with episodes of acute rejection, chronic rejection, and graft loss. Thus, monitoring for such antibodies is an important aspect of patient care.

The development of solid-phase antibody detection assays significantly enhanced our ability to identify HLA antibodies, taking virtual crossmatching from concept to reality. At the root of these detection assays are two questions that have been asked for almost 50 years: are donor-directed HLA antibodies present and, if so, are they clinically relevant? While the technology related to solid-phase antibody detection has seemingly allowed the first question to be answered with exquisite sensitivity and specificity, can the same be said for question 2?

Solid-phase antibody detection assays have clear benefits over historical approaches to antibody identification, but are not flawless. In fact, the limitations of these assays are frequently ignored. Herein, the strengths and weaknesses of solid-phase antibody detection are highlighted.