Kidney Week

Abstract: TH-PO998

Genome Wide Non HLA Alloimmunity Contributes to Graft Loss after Kidney Transplantation

Session Information

• Transplant Recipient Education, Adherence, and Novel Risk Factors for Graft Loss
  November 02, 2017 | Location: Hall H, Morial Convention Center
  Abstract Time: 10:00 AM - 10:00 AM

Category: Transplantation

• 1702 Transplantation: Clinical and Translational

Authors

• Oberbauer, Rainer, Medical University of Vienna, Vienna, Austria

Rainer Oberbauer,

• Reindl-Schwaighofer, Roman, Medical University of Vienna, Vienna, Austria

Roman Reindl-Schwaighofer,

• Kainz, Alexander, Department of Nephrology, Vienna, Austria

Alexander Kainz,

• Heinzel, Andreas, Medical University of Vienna, Vienna, Vienna, Austria

Andreas Heinzel,

• Jelencsics, Kira, Medical University Vienna, Vienna, Austria

Kira Jelencsics,

• Hruba, Petra, Institute for Clinical and Experimental Medicine, Prague, Czechia

Petra Hruba,

• Viklicky, Ondrej, Institute for Clinical and Experimental Medicine, Department of Nephrology, Prague, Czechia

Ondrej Viklicky,

• Bohmig, Georg, Medical University Vienna, Vienna, Austria

Georg Bohmig,

• Fischer, Gottfried, Medical University of Vienna, Vienna, Austria

Gottfried Fischer,

• Keating, Brendan, University of Pennsylvania, Philadelphia, Pennsylvania, United States

Brendan Keating,

Background

HLA alloimmunity is the main cause of renal transplant loss but the contribution of nonHLA donor recipient mismatches on a genome wide basis has not been elucidated thoroughly yet.

Methods

We made use of the iGeneTrain consortium and genotyped 753 donors and 863 corresponding recipients using the Affymetrix Axiom Tx GWAS Array (Affymetrix). Raw genotypes were after an initial quality control phased and imputed with impute2 using GoNL and 1KG data as reference panels. The ensemble Variant Effect Predictor and ANNOVAR were used for SNP annotation.
The number of recipients with a median follow up of 6.5 years were obtained from the Vienna and Prague transplant cohort study. The main available outcomes are death censored graft loss and eGFR slope after transplantation. HLA incompatibility and other clinical variables known to influence these outcomes are available.
In a first preliminary analysis elucidating the effect of donor recipient non-synonymous SNP (nsSNP) mismatches (MM) on graft survival a Cox model was employed to analyze the association of nsSNP MM with graft survival. For this preliminary analysis 180 donor recipient pairs with 36 events were available.

Results

The association of nsSNP MM with graft survival showed a trend towards elevated risk for death censored graft loss (table).


Table: Multivariable Cox model relating the time of graft survival to donor recipient HLA MM and nsSNP MM.
A follow up study utilizing the full cohort and imputation results will be performed in the next months prior to the meeting. Further custom peptide arrays (NimbleGen/Roche) holding 172,943 features will be employed to uncover the formation of antibodies in case of donor recipient LoF and nsSNP MM.

Conclusion

NonHLA alloimmunity independently contributes to graft loss after kidney transplantation.

Cox model