Alloantibody responses after renal transplant failure can be better predicted by donor-recipient HLA amino acid sequence and physicochemical disparities than conventional HLA matching
Taylor, Craig J
American Journal of Transplantation
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Kosmoliaptsis, V., Mallon, D., Chen, Y., Bolton, E., Bradley, J., & Taylor, C. J. (2016). Alloantibody responses after renal transplant failure can be better predicted by donor-recipient HLA amino acid sequence and physicochemical disparities than conventional HLA matching. American Journal of Transplantation, 16 2139-2147. https://doi.org/10.1111/ajt.13707
We have assessed whether HLA immunogenicity as defined by differences in donor-recipient HLA amino-acid sequence (amino-acid mismatch score, AMS; and eplet mismatch score, EpMS) and physicochemical properties (electrostatic mismatch score, EMS) enables prediction of allosensitisation to HLA, and also prediction of the risk of an individual donor-recipient HLA mismatch to induce donor-specific antibody (DSA). HLA antibody screening was undertaken using single-antigen beads in 131 kidney transplant recipients returning to the transplant waiting list following first graft failure. The effect of AMS, EpMS and EMS on the development of allosensitisation (calculated reaction frequency, cRF) and DSA was determined. Multivariate analyses, adjusting for time on the waiting list, maintenance on immunosuppression after transplant failure and graft nephrectomy, showed that AMS (OR: 1.44 per 10 units, 95% CI: 1.02-2.10, p=0.04) and EMS (OR: 1.27 per 10 38 units, 95% CI: 1.02-1.62, p=0.04) were independently associated with the risk of developing sensitisation to HLA (cRF>15%). AMS, EpMS and EMS were independently associated with the development of HLA-DR and HLA-DQ DSA, but only EMS correlated with the risk of HLA-A and -B DSA development. Differences in donor-recipient HLA amino-acid sequence and physicochemical properties enable better assessment of the risk of HLA-specific sensitisation than conventional HLA matching.
This study was supported by the Cambridge NIHR Biomedical Research Centre and the NIHR Blood and Transplant Research Unit in Organ Donation and Transplantation at the University of Cambridge in collaboration with Newcastle University and in partnership with NHS Blood and Transplant (NHSBT). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, the Department of Health or NHSBT . VK was supported by an Academy of Medical Sciences Grant and an Evelyn Trust Grant. DHM was supported by an RCSEng Research Fellowship.
External DOI: https://doi.org/10.1111/ajt.13707
This record's URL: https://www.repository.cam.ac.uk/handle/1810/253800