Improving organ allocation and protecting long-term graft function
The overall objective in this theme is to improve understanding of donor–recipient histocompatibility and to introduce novel interventions to improve long-term graft function. We are developing novel high-throughput techniques to type histocompatibility genes (human leukocyte antigen (HLA) and killer cell immunoglobulin-like receptors (KIR)). We utilise computational molecular modelling techniques, structural information from X-ray crystallography, and application of protein electrostatics theory to predict donor HLA immunogenicity, improve donor–recipient histocompatibility and inform organ allocation policy. We are also developing novel biophysical assays to characterise alloantibody–HLA interactions in real time and directly in patient sera to improve the assessment of transplant immunological risk and to enable early intervention before irreversible graft injury.
Theme Lead: Professor John Trowsdale
Senior researcher: Vasilis Kosmoliaptsis
Collaborations within the BTRU
Theme 6: With Professor Dave Collett (Theme 6 Lead and NHSBT Associate Director, Statistics and Clinical Studies) we are analysing national registry data to generate large-scale evidence for the introduction of a new UK-wide deceased-donor kidney allocation policy.
Theme 7: With Menna Clatworthy’s group we are characterizing KIR gene profiles in renal transplant patients who have been subject to immunological rejection.
Collaborations with academic partners
We are working with Professor Tuomas Knowles, Department of Chemistry, University of Cambridge, to develop a novel microfluidic platform to characterise alloantibody–HLA interactions in patient sera to reduce the detrimental effect of humoral alloimmunity on graft outcomes.
KIR-typing may allow identification of patients at high risk of transplant rejection. Better donor–recipient histocompatibility may improve long-term transplant outcomes and also improve access to transplantation by reducing recipient sensitisation (alloantibody development) to potential donors and by enabling allocation of organs to patients currently considered poor tissue matches. Similarly, better detection and characterisation of alloantibodies may enable early interventions after transplantation, before irreversible graft injury.
Other external funding
1. Jiang W, Johnson C, Simecek N, López-Álvarez MR, Di D, Trowsdale J, Traherne JA. qKAT: a high-throughput qPCR method for KIR gene copy number and haplotype determination. Genome Med. 2016 Sep 29; 8(1): 99 PubMed 27686127
2. Kosmoliaptsis V, Mallon DH, Chen Y, Bolton EM, Bradley JA, Taylor CJ. Alloantibody Responses After Renal Transplant Failure Can Be Better Predicted by Donor–Recipient HLA Amino Acid Sequence and Physicochemical Disparities Than Conventional HLA Matching. Am J Transplant. 2016 Jul; 16(7): 2139–47 PubMed 26755448
3. Wiebe C, Kosmoliaptsis V, Pochinco D, Taylor C, Nickerson P. A comparison of HLA molecular mismatch methods to determine HLA immunogenicity. Transplantation 2018 Feb 13 PubMed 29443827