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Determination of the clinical relevance of donor epitope-specific HLA-antibodies in kidney transplantation. 2024
Tineke Kardol-Hoefnagel, and
Danial Mohammadi Senejohnny, and
Elena G Kamburova, and
Bram W Wisse, and
Leon Reteig, and
Maartje L Gruijters, and
Irma Joosten, and
Wil A Allebes, and
Arnold van der Meer, and
Luuk B Hilbrands, and
Marije C Baas, and
Eric Spierings, and
Cornelis E Hack, and
Franka E van Reekum, and
Arjan D van Zuilen, and
Marianne C Verhaar, and
Michiel L Bots, and
Adriaan C A D Drop, and
Loes Plaisier, and
Rowena C A Melchers, and
Marc A J Seelen, and
Jan Stephan Sanders, and
Bouke G Hepkema, and
Annechien J A Lambeck, and
Laura B Bungener, and
Caroline Roozendaal, and
Marcel G J Tilanus, and
Christina E Voorter, and
Lotte Wieten, and
Elly M van Duijnhoven, and
Mariëlle A C J Gelens, and
Maarten H L Christiaans, and
Frans J van Ittersum, and
Shaikh A Nurmohamed, and
Neubury M Lardy, and
Wendy Swelsen, and
Karlijn A M I van der Pant, and
Neelke C van der Weerd, and
Ineke J M Ten Berge, and
Andries Hoitsma, and
Paul J M van der Boog, and
Johan W de Fijter, and
Michiel G H Betjes, and
Dave L Roelen, and
Frans H Claas, and
Frederike J Bemelman, and
Aleksandar Senev, and
Maarten Naesens, and
Sebastiaan Heidt, and
Henny G Otten
Center for Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
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.
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Elena G Kamburova, and
Bram W Wisse, and
Leon Reteig, and
Maartje L Gruijters, and
Irma Joosten, and
Wil A Allebes, and
Arnold van der Meer, and
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Mariëlle A C J Gelens, and
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Frans J van Ittersum, and
Shaikh A Nurmohamed, and
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Wendy Swelsen, and
Karlijn A M I van der Pant, and
Neelke C van der Weerd, and
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Andries Hoitsma, and
Paul J M van der Boog, and
Johan W de Fijter, and
Michiel G H Betjes, and
Dave L Roelen, and
Frans H Claas, and
Frederike J Bemelman, and
Aleksandar Senev, and
Maarten Naesens, and
Sebastiaan Heidt, and
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Maartje L Gruijters, and
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Wil A Allebes, and
Arnold van der Meer, and
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Eric Spierings, and
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Franka E van Reekum, and
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Michiel L Bots, and
Adriaan C A D Drop, and
Loes Plaisier, and
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Michiel G H Betjes, and
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Frans H Claas, and
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Aleksandar Senev, and
Maarten Naesens, and
Sebastiaan Heidt, and
Henny G Otten
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Leon Reteig, and
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Irma Joosten, and
Wil A Allebes, and
Arnold van der Meer, and
Luuk B Hilbrands, and
Marije C Baas, and
Eric Spierings, and
Cornelis E Hack, and
Franka E van Reekum, and
Arjan D van Zuilen, and
Marianne C Verhaar, and
Michiel L Bots, and
Adriaan C A D Drop, and
Loes Plaisier, and
Rowena C A Melchers, and
Marc A J Seelen, and
Jan Stephan Sanders, and
Bouke G Hepkema, and
Annechien J A Lambeck, and
Laura B Bungener, and
Caroline Roozendaal, and
Marcel G J Tilanus, and
Christina E Voorter, and
Lotte Wieten, and
Elly M van Duijnhoven, and
Mariëlle A C J Gelens, and
Maarten H L Christiaans, and
Frans J van Ittersum, and
Shaikh A Nurmohamed, and
Neubury M Lardy, and
Wendy Swelsen, and
Karlijn A M I van der Pant, and
Neelke C van der Weerd, and
Ineke J M Ten Berge, and
Andries Hoitsma, and
Paul J M van der Boog, and
Johan W de Fijter, and
Michiel G H Betjes, and
Dave L Roelen, and
Frans H Claas, and
Frederike J Bemelman, and
Aleksandar Senev, and
Maarten Naesens, and
Sebastiaan Heidt, and
Henny G Otten
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Danial Mohammadi Senejohnny, and
Elena G Kamburova, and
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Leon Reteig, and
Maartje L Gruijters, and
Irma Joosten, and
Wil A Allebes, and
Arnold van der Meer, and
Luuk B Hilbrands, and
Marije C Baas, and
Eric Spierings, and
Cornelis E Hack, and
Franka E van Reekum, and
Arjan D van Zuilen, and
Marianne C Verhaar, and
Michiel L Bots, and
Adriaan C A D Drop, and
Loes Plaisier, and
Rowena C A Melchers, and
Marc A J Seelen, and
Jan Stephan Sanders, and
Bouke G Hepkema, and
Annechien J A Lambeck, and
Laura B Bungener, and
Caroline Roozendaal, and
Marcel G J Tilanus, and
Christina E Voorter, and
Lotte Wieten, and
Elly M van Duijnhoven, and
Mariëlle A C J Gelens, and
Maarten H L Christiaans, and
Frans J van Ittersum, and
Shaikh A Nurmohamed, and
Neubury M Lardy, and
Wendy Swelsen, and
Karlijn A M I van der Pant, and
Neelke C van der Weerd, and
Ineke J M Ten Berge, and
Andries Hoitsma, and
Paul J M van der Boog, and
Johan W de Fijter, and
Michiel G H Betjes, and
Dave L Roelen, and
Frans H Claas, and
Frederike J Bemelman, and
Aleksandar Senev, and
Maarten Naesens, and
Sebastiaan Heidt, and
Henny G Otten
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Danial Mohammadi Senejohnny, and
Elena G Kamburova, and
Bram W Wisse, and
Leon Reteig, and
Maartje L Gruijters, and
Irma Joosten, and
Wil A Allebes, and
Arnold van der Meer, and
Luuk B Hilbrands, and
Marije C Baas, and
Eric Spierings, and
Cornelis E Hack, and
Franka E van Reekum, and
Arjan D van Zuilen, and
Marianne C Verhaar, and
Michiel L Bots, and
Adriaan C A D Drop, and
Loes Plaisier, and
Rowena C A Melchers, and
Marc A J Seelen, and
Jan Stephan Sanders, and
Bouke G Hepkema, and
Annechien J A Lambeck, and
Laura B Bungener, and
Caroline Roozendaal, and
Marcel G J Tilanus, and
Christina E Voorter, and
Lotte Wieten, and
Elly M van Duijnhoven, and
Mariëlle A C J Gelens, and
Maarten H L Christiaans, and
Frans J van Ittersum, and
Shaikh A Nurmohamed, and
Neubury M Lardy, and
Wendy Swelsen, and
Karlijn A M I van der Pant, and
Neelke C van der Weerd, and
Ineke J M Ten Berge, and
Andries Hoitsma, and
Paul J M van der Boog, and
Johan W de Fijter, and
Michiel G H Betjes, and
Dave L Roelen, and
Frans H Claas, and
Frederike J Bemelman, and
Aleksandar Senev, and
Maarten Naesens, and
Sebastiaan Heidt, and
Henny G Otten
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Le Journal medical libanais. The Lebanese medical journal,
Tineke Kardol-Hoefnagel, and
Danial Mohammadi Senejohnny, and
Elena G Kamburova, and
Bram W Wisse, and
Leon Reteig, and
Maartje L Gruijters, and
Irma Joosten, and
Wil A Allebes, and
Arnold van der Meer, and
Luuk B Hilbrands, and
Marije C Baas, and
Eric Spierings, and
Cornelis E Hack, and
Franka E van Reekum, and
Arjan D van Zuilen, and
Marianne C Verhaar, and
Michiel L Bots, and
Adriaan C A D Drop, and
Loes Plaisier, and
Rowena C A Melchers, and
Marc A J Seelen, and
Jan Stephan Sanders, and
Bouke G Hepkema, and
Annechien J A Lambeck, and
Laura B Bungener, and
Caroline Roozendaal, and
Marcel G J Tilanus, and
Christina E Voorter, and
Lotte Wieten, and
Elly M van Duijnhoven, and
Mariëlle A C J Gelens, and
Maarten H L Christiaans, and
Frans J van Ittersum, and
Shaikh A Nurmohamed, and
Neubury M Lardy, and
Wendy Swelsen, and
Karlijn A M I van der Pant, and
Neelke C van der Weerd, and
Ineke J M Ten Berge, and
Andries Hoitsma, and
Paul J M van der Boog, and
Johan W de Fijter, and
Michiel G H Betjes, and
Dave L Roelen, and
Frans H Claas, and
Frederike J Bemelman, and
Aleksandar Senev, and
Maarten Naesens, and
Sebastiaan Heidt, and
Henny G Otten
January 2009,
Contributions to nephrology,
Tineke Kardol-Hoefnagel, and
Danial Mohammadi Senejohnny, and
Elena G Kamburova, and
Bram W Wisse, and
Leon Reteig, and
Maartje L Gruijters, and
Irma Joosten, and
Wil A Allebes, and
Arnold van der Meer, and
Luuk B Hilbrands, and
Marije C Baas, and
Eric Spierings, and
Cornelis E Hack, and
Franka E van Reekum, and
Arjan D van Zuilen, and
Marianne C Verhaar, and
Michiel L Bots, and
Adriaan C A D Drop, and
Loes Plaisier, and
Rowena C A Melchers, and
Marc A J Seelen, and
Jan Stephan Sanders, and
Bouke G Hepkema, and
Annechien J A Lambeck, and
Laura B Bungener, and
Caroline Roozendaal, and
Marcel G J Tilanus, and
Christina E Voorter, and
Lotte Wieten, and
Elly M van Duijnhoven, and
Mariëlle A C J Gelens, and
Maarten H L Christiaans, and
Frans J van Ittersum, and
Shaikh A Nurmohamed, and
Neubury M Lardy, and
Wendy Swelsen, and
Karlijn A M I van der Pant, and
Neelke C van der Weerd, and
Ineke J M Ten Berge, and
Andries Hoitsma, and
Paul J M van der Boog, and
Johan W de Fijter, and
Michiel G H Betjes, and
Dave L Roelen, and
Frans H Claas, and
Frederike J Bemelman, and
Aleksandar Senev, and
Maarten Naesens, and
Sebastiaan Heidt, and
Henny G Otten
May 2015,
Clinical transplantation,
