Clinical relevance of circulating donor-specific HLA antibodies

For a long period of time complement-dependent cytotoxicity was the standard assay to demonstrate clinically relevant HLA antibodies in the serum of patients before transplantation. The introduction of more sensitive solid-phase assays to detect HLA antibodies had led to a lot of discussion on the clinical relevance of the presence of these antibodies before transplantation and the appearance of these antibodies after transplantation. This review discusses the current controversies.

The old dogma that the presence of donor-specific HLA antibodies before transplantation is a contra-indication for transplantation does not exist anymore. The correlation between the presence of HLA antibodies and clinical outcome is less strict although the presence of circulating donor-specific antibodies, both before and after transplantation, should be considered a risk factor. It is clear, however, that the opinion on the clinical relevance of donor-specific HLA antibodies is very different amongst the transplant centers.

The clinical relevance of the presence of donor-specific HLA antibodies before transplantation and the appearance of these antibodies after transplantation is a controversial issue. The lack of consensus between different centers is partly due to the heterogeneity of the HLA antibodies involved. Standardization is essential and future studies must focus on the further characterization of the antibody titers, the immunoglobulin (sub)classes of the antibodies and the epitopes recognized. It remains to be established in which cases the HLA antibodies are the direct cause of or just associated with (chronic) graft failure.