Anti-allograft antibodies: some are harmful, some can be overcome, and some may be beneficial

Up to one third of candidates for organ or hematopoietic stem cell transplantation in the United States have antibodies to histocompatibility antigens, the most problematic of which are those of the HLA genetic system. The presence of high levels of HLA-specific antibodies reduces access to transplantation as a treatment option for many patients, and, for others with lower levels, increases the risk of rejection and impacts long term graft survival. Other polymorphic antigens, as well as some autologous antigens, have also been implicated in antibody mediated rejection and may act in concert or synergy with HLA-specific antibodies. The degree of risk imposed by antibodies correlates with their level or strength, with low levels evoking less damage and under some circumstances perhaps even offering some protective benefit. Clinical protocols now provide options for overcoming or circumventing humoral sensitization while research on the signaling pathways triggered by antibodies binding to their target antigens may lead to improved options for therapeutic intervention.