TY - JOUR
T1 - Determination of the clinical relevance of donor epitope-specific HLA-antibodies in kidney transplantation
AU - Kardol-Hoefnagel, Tineke
AU - Senejohnny, Danial Mohammadi
AU - Kamburova, Elena G.
AU - Wisse, Bram W.
AU - Reteig, Leon
AU - Gruijters, Maartje L.
AU - Joosten, Irma
AU - Allebes, Wil A.
AU - van der Meer, Arnold
AU - Hilbrands, Luuk B.
AU - Baas, Marije C.
AU - Spierings, Eric
AU - Hack, Cornelis E.
AU - van Reekum, Franka E.
AU - van Zuilen, Arjan D.
AU - Verhaar, Marianne C.
AU - Bots, Michiel L.
AU - Drop, Adriaan C. A. D.
AU - Plaisier, Loes
AU - Melchers, Rowena C. A.
AU - Seelen, Marc A. J.
AU - Sanders, Jan Stephan
AU - Hepkema, Bouke G.
AU - Lambeck, Annechien J. A.
AU - Bungener, Laura B.
AU - Roozendaal, Caroline
AU - Tilanus, Marcel G. J.
AU - Voorter, Christina E.
AU - Wieten, Lotte
AU - van Duijnhoven, Elly M.
AU - Gelens, Mariëlle A. C. J.
AU - Christiaans, Maarten H. L.
AU - van Ittersum, Frans J.
AU - Nurmohamed, Shaikh A.
AU - Lardy, Neubury M.
AU - Swelsen, Wendy
AU - van der Pant, Karlijn A. M. I.
AU - van der Weerd, Neelke C.
AU - ten Berge, Ineke J. M.
AU - Hoitsma, Andries
AU - van der Boog, Paul J. M.
AU - de Fijter, Johan W.
AU - Betjes, Michiel G. H.
AU - Roelen, Dave L.
AU - Claas, Frans H.
AU - Bemelman, Frederike J.
AU - Senev, Aleksandar
AU - Naesens, Maarten
AU - Heidt, Sebastiaan
AU - Otten, Henny G.
N1 - Publisher Copyright: © 2024 The Authors. HLA: Immune Response Genetics published by John Wiley & Sons Ltd.
PY - 2024/1/1
Y1 - 2024/1/1
N2 - In kidney transplantation, survival rates are still partly impaired due to the deleterious effects of donor specific HLA antibodies (DSA). However, not all luminex-defined DSA appear to be clinically relevant. Further analysis of DSA recognizing polymorphic amino acid configurations, called eplets or functional epitopes, might improve the discrimination between clinically relevant vs. irrelevant HLA antibodies. To evaluate which donor epitope-specific HLA antibodies (DESAs) are clinically important in kidney graft survival, relevant and irrelevant DESAs were discerned in a Dutch cohort of 4690 patients using Kaplan–Meier analysis and tested in a cox proportional hazard (CPH) model including nonimmunological variables. Pre-transplant DESAs were detected in 439 patients (9.4%). The presence of certain clinically relevant DESAs was significantly associated with increased risk on graft loss in deceased donor transplantations (p < 0.0001). The antibodies recognized six epitopes of HLA Class I, 3 of HLA-DR, and 1 of HLA-DQ, and most antibodies were directed to HLA-B (47%). Fifty-three patients (69.7%) had DESA against one donor epitope (range 1–5). Long-term graft survival rate in patients with clinically relevant DESA was 32%, rendering DESA a superior parameter to classical DSA (60%). In the CPH model, the hazard ratio (95% CI) of clinically relevant DESAs was 2.45 (1.84–3.25) in deceased donation, and 2.22 (1.25–3.95) in living donation. In conclusion, the developed model shows the deleterious effect of clinically relevant DESAs on graft outcome which outperformed traditional DSA-based risk analysis on antigen level.
AB - In kidney transplantation, survival rates are still partly impaired due to the deleterious effects of donor specific HLA antibodies (DSA). However, not all luminex-defined DSA appear to be clinically relevant. Further analysis of DSA recognizing polymorphic amino acid configurations, called eplets or functional epitopes, might improve the discrimination between clinically relevant vs. irrelevant HLA antibodies. To evaluate which donor epitope-specific HLA antibodies (DESAs) are clinically important in kidney graft survival, relevant and irrelevant DESAs were discerned in a Dutch cohort of 4690 patients using Kaplan–Meier analysis and tested in a cox proportional hazard (CPH) model including nonimmunological variables. Pre-transplant DESAs were detected in 439 patients (9.4%). The presence of certain clinically relevant DESAs was significantly associated with increased risk on graft loss in deceased donor transplantations (p < 0.0001). The antibodies recognized six epitopes of HLA Class I, 3 of HLA-DR, and 1 of HLA-DQ, and most antibodies were directed to HLA-B (47%). Fifty-three patients (69.7%) had DESA against one donor epitope (range 1–5). Long-term graft survival rate in patients with clinically relevant DESA was 32%, rendering DESA a superior parameter to classical DSA (60%). In the CPH model, the hazard ratio (95% CI) of clinically relevant DESAs was 2.45 (1.84–3.25) in deceased donation, and 2.22 (1.25–3.95) in living donation. In conclusion, the developed model shows the deleterious effect of clinically relevant DESAs on graft outcome which outperformed traditional DSA-based risk analysis on antigen level.
KW - donor epitope specific antibodies
KW - graft survival
KW - kidney transplantation
UR - http://www.scopus.com/inward/record.url?scp=85182701812&partnerID=8YFLogxK
U2 - https://doi.org/10.1111/tan.15346
DO - https://doi.org/10.1111/tan.15346
M3 - Article
C2 - 38239046
SN - 2059-2302
VL - 103
JO - HLA
JF - HLA
IS - 1
M1 - e15346
ER -