Solid Phase-Based Cross-Matching in Order to Avoid Kidney Allografting against Donor-Specific Anti-HlA Antibodies: Long Term Experience with a Procedure Allowing Highly Reliable Diagnoses

Transplant recipients with sensitizing events such as previous transplants, blood transfusions or pregnancies often develop antibodies which are directed against Human Leukocyte Antigen (HLA)-molecules of the donor tissue. These preformed Donor-Specific Anti-HLA Antibodies (DSA) represent a high risk of allograft failure due to antibody-mediated hyper-acute or acute rejection. In order to select recipients without these detrimental DSA, the Complement- Dependent Cytotoxicity Assay (CDC) was developed more than forty years ago and established as standard crossmatch technique. However, as a functional i.e. vitality assay it detects only those antibodies which exert their detrimental function through their complement-activating features and fails to identify DSA which lack complement-fixing activity although these may as well be detrimental for the allograft survival. Furthermore, the outcome strongly depends on the availability of isolated vital lymphocytes sometimes not available of a given donor. In addition, pharmacological treatment as well as underlying diseases may lead to artificially positive results of the CDC demonstrating this assay's general insufficiency under certain circumstances. As a consequence alternative solid phase-based crossmatch assays which function independently of the cell quality had been generated in order to detect DSA and were implemented in our laboratory about nine years ago. We here review the results of these assays and the conclusions to be drawn for special groups of patients on the kidney waiting list of our tissue typing laboratory. The data clearly demonstrate the superiority of the alternative Enzyme-Linked Immunosorbent Assay (ELISA)- based techniques when compared with the CDC-crossmatch not leading to valid results under various circumstances.