Determination of the clinical relevance of donor epitope-specific HLA-antibodies in kidney transplantation

Tineke Kardol-Hoefnagel*, Danial Mohammadi Senejohnny, Elena G. Kamburova, Bram W. Wisse, Leon Reteig, Maartje L. Gruijters, Irma Joosten, Wil A. Allebes, Arnold van der Meer, Luuk B. Hilbrands, Marije C. Baas, Eric Spierings, Cornelis E. Hack, Franka E. van Reekum, Arjan D. van Zuilen, Marianne C. Verhaar, Michiel L. Bots, Adriaan C.A.D. Drop, Loes Plaisier, Rowena C.A. MelchersMarc A.J. Seelen, Jan Stephan Sanders, Bouke G. Hepkema, Annechien J.A. Lambeck, Laura B. Bungener, Caroline Roozendaal, Marcel G.J. Tilanus, Christina E. Voorter, Lotte Wieten, Elly M. van Duijnhoven, Mariëlle A.C.J. Gelens, Maarten H.L. Christiaans, Frans J. van Ittersum, Shaikh A. Nurmohamed, Neubury M. Lardy, Wendy Swelsen, Karlijn A.M.I. van der Pant, Neelke C. van der Weerd, Ineke J.M. ten Berge, Andries Hoitsma, Paul J.M. van der Boog, Johan W. de Fijter, Michiel G.H. Betjes, Dave L. Roelen, Frans H. Claas, Frederike J. Bemelman, Aleksandar Senev, Maarten Naesens, Sebastiaan Heidt, Henny G. Otten*

*Corresponding author voor dit werk

OnderzoeksoutputAcademicpeer review

1 Citaat (Scopus)
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Samenvatting

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.

Originele taal-2English
Artikelnummere15346
Aantal pagina's14
TijdschriftHLA
Volume103
Nummer van het tijdschrift1
Vroegere onlinedatum18-jan.-2024
DOI's
StatusPublished - jan.-2024

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