Advances in pre- and posttransplant immunologic testing in kidney transplantation

Abstract

Pre- and posttransplant risk estimation in kidney transplantation is important for the selection of appropriate treatment strategies. Recently, using new immunologic tests, we made observations within the framework of the Collaborative Transplant Study that may influence clinical practice. Complement-dependent lymphocytotoxic panel reactivity as a measure of anti-HLA sensitization, although criticized for its low sensitivity, is a useful indicator of an increased risk of rejection. Using the more sensitive complement-independent ELISA methodology, which utilizes solubilized HLA molecules instead of lymphocytes, we found that recipients with preformed complement-dependent anti-HLA antibodies showed a decreased graft survival only if their antibodies were directed against both HLA class I and class II, whereas isolated reactivity only against HLA class I or class II was of no clinical consequence. Pretransplant serum-soluble CD30 (sCD30) was found to be an independent and highly predictive factor of immunologic risk. The effects of sCD30 and anti-HLA antibodies were additive. Importantly, even patients without anti-HLA antibodies showed a strong HLA matching effect if their pretransplant serum contained high levels of sCD30. Although the role of anti-HLA antibody formation after transplantation remains uncertain, ELISA-detected sCD30 was shown to indicate impending graft rejection as early as on posttransplant days 3 to 5. Another very sensitive indicator of impending rejection is provided by posttransplant monitoring of the cytotoxic T-lymphocyte effector genes, perforin and granzyme B, in peripheral blood using real-time PCR.