Monitoring and treating posttransplant human leukocyte antigen antibodies

The important role of preformed human leukocyte antigen (HLA) antibodies in the outcome of organ transplants has been well demonstrated for the past 40 years. During this same period, the significance of HLA antibody formation after transplantation was largely ignored. Only in the past 10 years has become increasingly clear that HLA antibodies formed posttransplantation are the major cause of allograft failure. We provide here an updated review of the critical evidence implicating HLA antibodies in chronic rejection. It has now also been shown that antibodies formed soon after transplantation are much more toxic to the graft than antibodies formed after the first year. This is likely a result of adaptation of the graft after the first year, possibly through endothelial cell replacement. On the basis of this new finding, a policy of monitoring for antibody development after 3, 6, 9, and 12 months, with yearly checks thereafter, is suggested. Another important new development is the use of bortezomib, a fresh new agent for the removal of antibodies. Because this is the first agent to act on plasma cells, its use is promising. Early data on successful removal of antibodies are reviewed here.