Laboratory assessment of HLA antibodies circa 2006: making sense of sensitivity

For recipients of solid organs, such as kidneys and hearts, a major risk factor for graft rejection/graft loss is the presence of donor-directed HLA antibodies. The pre-transplant selection of donor:recipient pairs and the course of therapy posttransplant are influenced by the patients' antibody status. In the past, antibody assignments were performed exclusively with lymphocyte targets in complement dependent cytotoxicity assays. However, these assays were relatively nonspecific (positive reactions could be due to non-HLA antibodies) and insensitive (false-negative reactions). The recent development of solid-phase antibody detection assays, coupled with the application of flow-cytometric technology, has revolutionized our ability to sensitively and specifically define HLA antibodies. In this review, we chronicle the evolution of antibody detection assays and discuss the clinical relevance of HLA antibodies defined by current approaches.