Identification of clinically relevant HLA alloantibodies
Research type
Research Study
Full title
Investigation of the clinical significance of HLA-specific antibody binding kinetics in kidney transplantation
IRAS ID
167211
Contact name
Vasilis Kosmoliaptsis
Contact email
Sponsor organisation
Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge
Duration of Study in the UK
1 years, 0 months, 1 days
Research summary
Early results following kidney transplantation are excellent, however, many kidneys fail later due to the development of antibodies that attack the transplanted organ. Antibodies in transplant recipients are directed against donor-expressed Human Leukocyte Antigen (HLA) molecules. The risk of antibody-mediated rejection can be offset by ensuring donor kidneys are allocated to recipients with a good tissue-match. However, due to extensive variability of human HLA molecules, kidney transplantation commonly leads to HLA-directed antibody development that can induce graft injury and increase the requirement for use of strong immunosuppression regimens.
Currently, the presence of HLA antibodies in patient blood samples is detected using increasingly sensitive laboratory techniques, such as the Luminex Single Antigen Bead system. This system has improved organ allocation and post-transplant monitoring, however, a shortcoming of this increased sensitivity in antibody detection is that, often, clinically important antibodies cannot be distinguished from clinically irrelevant antibodies. Consequently, a patient may be unnecessarily denied a kidney transplant (where a clinically unimportant antibody is detected), or a recipient may receive an organ that succumbs to rapid antibody-mediated rejection (where a clinically relevant antibody, present only at low level, is overlooked).
Using blood samples from patients on the organ transplant waiting list with pre-formed antibodies against HLA molecules, we will determine the affinity, or strength, of binding. We anticipate that the binding affinity is a more informative parameter on which to assess the clinical significance of alloantibodies.This research has the potential to increase access to kidney transplantation for highly-sensitised patients and lead to improved long term outcomes. Timely detection of clinically relevant HLA antibodies following kidney transplantation may enable tailoring of immunosuppression regimens to individual patients minimising the detrimental effects of both rejection and over-immunosuppression on long-term graft and patient outcomes.
REC name
North East - York Research Ethics Committee
REC reference
15/NE/0081
Date of REC Opinion
27 Feb 2015
REC opinion
Favourable Opinion