Optimisation of histocompatibility testing in living-donor renal transplantation

The study addressed the development and evaluation of novel procedures for the rapid, reproducible and efficient measurement of T cell alloreactivity both pre- and post-transplantation, with the aim of optimizing donor/ recipient compatibility in renal transplantation. Furthermore, a comparison of the three currently available procedures for the detection of cytotoxic antibodies to determine which of these is best suited to optimizing pre-transplantation donor-recipient matching, as well as post-transplantation detection of sensitization to donor alloantigens. She established that the standard CDC crossmatching (CDCXM) had a high false-positive rate and that the Donor specific antigen crossmatch (DSAXM) method delivered the most accurate results for identifying anti-HLA antibodies in prospective, pre-sensitised kidney transplant patients. Cytokine profile analysis identified the involvement of eosinophils and a marked increase of anti-inflammatory cytokines that may possibly contribute to the initiation of kidney transplant rejection. Finally, she has shown that, the use of novel, CFSE-based two-way mixed lymphocyte cultures (MLC) adapted for flow cytometry may be able to identify patients that are at risk of transplant rejection. Furthermore, this novel method may possibly be the test of choice to indicate probable graft-versus-host-disease (GVHD) incidences. The overall findings of the study may contribute to optimising histocompatibility testing in renal transplantation by improving HLA matching criteria as well as identifying potential strategies to monitor and prevent GVHD.Thesis (PhD)--University of Pretoria, 2018.National Health Laboratory Services Research TrustImmunologyPhDUnrestricte