Molecular HLA matching in paediatric kidney transplantation

• Research type

  Research Study

• Full title

  Transplant for Life – Advancing HLA Matching in Paediatric Kidney Transplantation using Molecular Assessment of HLA Immunogenicity

• IRAS ID

  284167

• Clinicaltrials.gov Identifier

  MR/V037900/1 , MRC Cllinical Academic Research Partnership; APP1184595; 2020-2023, National Health and Medical Research Council (NHMRC) Ideas Grant

• Duration of Study in the UK

  3 years, 0 months, 1 days

• Research summary

  Kidney transplantation is the best treatment for children and young people with kidney failure. Transplants only last 12-15 years on average and the main cause of transplant failure is damage due to rejection by the body’s immune system. The recipient recognises the transplant as a foreign object due to differences in HLA type. HLA typing was previously classified using broad categories called serotypes. This dates back to when HLA typing was done using antibodies from patients sensitised through blood transfusions or previous pregnancies. HLA typing can now be done using genetic sequencing. This enables detailed comparison of the whole protein using modern computer algorithms (molecular HLA matching). Our team has developed a novel method which is based on 3D models and electrostatic charge at the surface of the HLA structure. We also compute the interaction between T-cells and B-cells; both of which are needed to produce antibodies and rejection.

  In this three-part study, we will compare molecular HLA matching to current serology matching in predicting rejection and transplant survival in paediatric patients. This study is based on clinical information in the NHS Blood and Transplant (NHSBT) registry. Work Package (WP) 1: The algorithm will be designed to predict rejection and 50% decline in transplant function. To develop the algorithm, we will analysis an in-depth cohort from 2010-2015. HLA typing will be repeated using next generation sequencing. Specific additional data will be collected from local records and uploaded to the registry. Biopsy results and post-transplant antibodies will be reanalysed centrally. WP2: We will test the ability of the algorithm to predict transplant failure using registry data alone in a larger cohort from 2000-2015. WP3: In patients with failed transplants, we will use the algorithm to predict the level of HLA sensitisation and the waiting time for their next transplant.

• REC name

  East Midlands - Derby Research Ethics Committee

• REC reference

  21/EM/0175

• Date of REC Opinion

  10 Aug 2021

• REC opinion

  Favourable Opinion