Current strategies to improve graft outcome following kidney transplantation consider information at the HLA loci. We asked whether information outside of the HLA loci can also impact long-term graft function (LTGF).

We used exome sequencing of DNA from kidney graft recipients (R) and their living donors (D) to determine R/D mismatches at the amino acid level over entire exomes. We estimated the number of amino acid mismatches in transmembrane proteins, more likely to be seen as foreign by the recipient's immune system, and designated this tally as the allogenomics mismatch score (AMS). The AMS can be measured prior to transplantation with DNA for potential donor and recipient pairs. We examined the degree of relationship between the AMS and post-transplantation kidney allograft function using mixed models, considering transplants from three independent cohorts (total 106 exomes, 53 pairs, 239 observations of estimated glomerular filtration rate (eGFR). We found that the AMS has a significant and consistent effect on eGFR effect size across the entire range of the score: -19.4 [-37.7, -1.1], P=0.0042, [chi]2= 8.1919, d.f.=1) that is independent of the HLA effect, donor age, and time post-transplantation.

Conclusion: These results show that the AMS is a strong and robust predictor of LTGF in kidney transplant recipients independently of HLA loci. They indicate that graft function can also be influenced by R/D mismatches in sets of genes whose identity varies for each R/D pair.

CITATION INFORMATION: Mesnard L, Muthukumar T, Burbach M, Li C, Shang H, Dadhania D, Lee J, Sharma V, Xiang J, Carmagnat M, Suberbielle C, Ouali N, Rondeau E, Friedewald J, Abecassis M, Suthanthiran M, Campagne F. Exome Sequencing and HLA-Independent Prediction of Long-Term Kidney Allograft Function. Am J Transplant. 2016;16 (suppl 3).

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