Predicted Indirectly ReCognizable HLA epitopes presented by HLA-DRB1 (PIRCHE-II), a novel tool to identify permissible HLA mismatches in kidney transplantation

K. Geneugelijk, M. Niemann, J. Drylewicz, A.D van Zuilen, I. Joosten, W.A. Allebes, A. van der Meer, L.B. Hilbrands, M.C. Baas, C.E. Hack, F.E. van Reekum, M.C. Verhaar, E.G. Kamburova, M.L. Bots, M.A.J Seelen, J.S. Sanders, B.G Hepkema, A.J. Lambeck, L.B. Bungener, C. Roozendaal, M.G.J. Tilanus, J. Vanderlocht, C.E. Voorter, L. Wieten, E.M. van Duijnhoven, M.A.C.J. Gelens, M.H.L. Christiaans, F. van Ittersum, A. Nurmohamed, N.M. Lardy, W.T. Swelsen, K.A.M.I. van der Pant, N.C van der Weerd, I.J.M. ten Berge, F.J. Bemelman, A.J. Hoitsma, P.J.M van der Boog, J.W. de Fijter, M.G.H. Betjes, S. Heidt, D.L. Roelen, F.H.J. Claas, H.G. Otten, E. Spierings

Chair(s): Prof. dr. L.B. Hilbrands & dr. H.M. Kwakkel-van Erp

Wednesday 8 march 2017

18:30 - 18:42h at Willem Pijperzaal

Categories: Parallel - Klinisch

Parallel session: Parallelsessie VI - Klinisch 1 - HLA-antilichamen en immunomodulatie

Individual HLA mismatches may have differential effects on graft survival after kidney transplantation. Therefore, there is a need for a reliable tool to define permissible HLA mismatches in kidney transplantation. We previously demonstrated that Predicted Indirectly ReCognizable HLA epitopes of donor origin presented by recipient HLA class-II (PIRCHE-II) play a role in de novo DSA formation after kidney transplantation. In the present Dutch multi-center study we evaluated the possible association between PIRCHE-II and kidney graft failure in 3,061 donor-recipient couples that were transplanted between 1995 and 2005. For these donors-recipients couples, PIRCHE-II was determined and was related to graft survival in both univariate and multivariable analyses. Adjusted for confounders, the natural logarithm of PIRCHE-II was associated with a higher risk for graft failure (HR:1.11, 95% CI:1.04-1.17, p=0.001). Univariately analyzed, patients with low PIRCHE-II numbers had a better 10-years graft survival than patients with higher PIRCHE-II numbers (p=0.001; PIRCHE-II strata: <9, ≥9-<35, ≥35-<90, and ≥90 with 82%, 76%, 73%, and 70% 10-year graft survival). Our data suggest that the PIRCHE-II algorithm is a valuable tool to discriminate between permissible HLA mismatches and high-risk HLA mismatches in kidney transplantation. Inclusion of PIRCHE-II in donor-selection criteria may eventually lead to an improved kidney graft survival.