The role of HLA-C in renal transplantation

Koh, Hoey C. (2016) The role of HLA-C in renal transplantation. MSc(R) thesis, University of Glasgow.

Abstract

Background:
Kidney transplantations have been traditionally been allocated based on matching results of HLA-A, HLA-B and HLA-DR. These have historically been considered pivotal to successful outcomes in kidney transplantation. There is a difference of 21% in 10-year survival between best and worst matched categories, which would suggest other factors, both immunological and non-immunological factors, may contribute to transplant outcome. With advances in immunosuppression treatment, HLA matching has been abolished in some parts of the world to hopefully offset the issue on lack of organ availability and also to eliminate the risks from prolonged cold ischaemic time as a result of increasing geographical distances between donors and recipients.

Increasing evidence implicates emergent anti-HLA antibody with long-term graft loss and often these antibodies are directed against immunological factors out with the routinely matched HLA-A, -HLA-B and HLA-DR, for example HLA-C. There are some studies which suggest that HLA-C has an impact on outcome of renal transplantation, perhaps through its role in modulation of natural killer cells.

The objective of this study is to determine if matching of HLA-C affects acute rejection, graft survival and patient survival in renal transplantation.

Methods:
This is a retrospective cohort study conducted on all consecutive renal transplantations performed at the Glasgow Renal and Transplant Unit from 2007 to 2011. Baseline demographic, recipient and donor data, clinical data as well as immunological data were obtained from prospectively collected database.

Univariate descriptive statistics were utilised to characterise patient baseline demographic and clinical data. Categorical variables were summarised using contingency tables and Chi-square statistics. For continuous variables, basic univariate statistics were used to report the data and T-tests were used to compare the mean. Time-dependent Cox regression analysis was used to assess acute rejection, graft loss, patient survival and overall patient survival in relation to renal graft loss and acute rejection. All statistical analyses were performed using SPSS version 16.0.

Results:
The results of the study unfortunately did not show any significant impact of HLA-A, B, DR and C matching or compatibility on the outcomes of renal transplantation. Typing for the traditional MHC I and II antigens still plays a role in helping to prioritise kidney allocations in the United Kingdom as this minimises the risk of sensitisation and development of antibodies which could potentially affect future transplantation especially in young patients who are more than likely to out-live their allografts.

To improve the quality of the study will require a prospective data collection, as well as to include other potential confounders (such as type of deceased donors, urinary sepsis, BK nephropathy, CMV infection or CNI toxicity) in a prospectively run cohort study. Other interesting aspects of HLA-C (such as its role as inhibitory KIR ligands of NK cells), could also be looked into in future studies.

Conclusion:
This study has not shown a significant role of HLA-C matching in renal transplantation. The potential of HLA-C DSA should however be kept in mind in patients who suffer from acute antibody-mediated rejections as this could impact the planning of future re-transplantations.

• Item Type: Thesis (MSc(R))
• Qualification Level: Masters
• Additional Information: Due to copyright restrictions the full text of this thesis cannot be made available online. Access to the printed version is available.
• Keywords: HLA-C; renal transplantation
• Subjects: R Medicine > R Medicine (General)
• Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Supervisor's Name: Horgan, Professor Paul and Clancy, Mr. Marc
• Date of Award: 2016
• Depositing User: Miss Hoey C. Koh
• Unique ID: glathesis:2016-7035
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 18 Jan 2016 14:23
• Last Modified: 03 Mar 2016 15:06
• URI: https://theses.gla.ac.uk/id/eprint/7035