Frontiers in Immunology (Dec 2018)
Development and Validation of a Multiplex Non-HLA Antibody Assay for the Screening of Kidney Transplant Recipients
- Elena G. Kamburova,
- Tineke Kardol-Hoefnagel,
- Bram W. Wisse,
- 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,
- Jan Meeldijk,
- Niels Bovenschen,
- Niels Bovenschen,
- Marc 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,
- Frederike J. Bemelman,
- Paul J. M. van der Boog,
- Johan W. de Fijter,
- Michiel G. H. Betjes,
- Sebastiaan Heidt,
- Dave L. Roelen,
- Frans H. Claas,
- Henny G. Otten
Affiliations
- Elena G. Kamburova
- Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands
- Tineke Kardol-Hoefnagel
- Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands
- Bram W. Wisse
- Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands
- Irma Joosten
- Laboratory Medicine, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, Netherlands
- Wil A. Allebes
- Laboratory Medicine, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, Netherlands
- Arnold van der Meer
- Laboratory Medicine, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, Netherlands
- Luuk B. Hilbrands
- Department of Nephrology, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, Netherlands
- Marije C. Baas
- Department of Nephrology, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, Netherlands
- Eric Spierings
- Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands
- Cornelis E. Hack
- Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands
- Franka E. van Reekum
- Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, Netherlands
- Arjan D. van Zuilen
- Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, Netherlands
- Marianne C. Verhaar
- Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, Netherlands
- Michiel L. Bots
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands
- Adriaan C. A. D. Drop
- Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands
- Loes Plaisier
- Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands
- Jan Meeldijk
- Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands
- Niels Bovenschen
- Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands
- Niels Bovenschen
- Department of Pathology, University Medical Center Utrecht, Utrecht, Netherlands
- Marc A. J. Seelen
- Department of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
- Jan Stephan Sanders
- Department of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
- Bouke G. Hepkema
- Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
- Annechien J. A. Lambeck
- Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
- Laura B. Bungener
- Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
- Caroline Roozendaal
- Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
- Marcel G. J. Tilanus
- Tissue Typing Laboratory, Department of Transplantation Immunology, Maastricht University Medical Center, Maastricht, Netherlands
- Christina E. Voorter
- Tissue Typing Laboratory, Department of Transplantation Immunology, Maastricht University Medical Center, Maastricht, Netherlands
- Lotte Wieten
- Tissue Typing Laboratory, Department of Transplantation Immunology, Maastricht University Medical Center, Maastricht, Netherlands
- Elly M. van Duijnhoven
- 0Division of Nephrology, Department of Internal Medicine, Maastricht University Medical Center, Maastricht, Netherlands
- Mariëlle A. C. J. Gelens
- 0Division of Nephrology, Department of Internal Medicine, Maastricht University Medical Center, Maastricht, Netherlands
- Maarten H. L. Christiaans
- 0Division of Nephrology, Department of Internal Medicine, Maastricht University Medical Center, Maastricht, Netherlands
- Frans J. van Ittersum
- 1Amsterdam University Medical Center, Department of Nephrology, Vrije Universiteit Amsterdam, Amsterdam, Netherlands
- Shaikh A. Nurmohamed
- 1Amsterdam University Medical Center, Department of Nephrology, Vrije Universiteit Amsterdam, Amsterdam, Netherlands
- Neubury M. Lardy
- 2Department of Immunogenetics, Sanquin Diagnostic Services, Amsterdam, Netherlands
- Wendy Swelsen
- 2Department of Immunogenetics, Sanquin Diagnostic Services, Amsterdam, Netherlands
- Karlijn A. M. I. van der Pant
- 3Renal Transplant Unit, Department of Internal Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands
- Neelke C. van der Weerd
- 3Renal Transplant Unit, Department of Internal Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands
- Ineke J. M. ten Berge
- 3Renal Transplant Unit, Department of Internal Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands
- Frederike J. Bemelman
- 3Renal Transplant Unit, Department of Internal Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands
- Paul J. M. van der Boog
- 4Department of Nephrology, Leiden University Medical Center, Leiden, Netherlands
- Johan W. de Fijter
- 4Department of Nephrology, Leiden University Medical Center, Leiden, Netherlands
- Michiel G. H. Betjes
- 5Department of Internal Medicine, Nephrology, Erasmus Medical Center, Rotterdam, Netherlands
- Sebastiaan Heidt
- 6Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, Netherlands
- Dave L. Roelen
- 6Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, Netherlands
- Frans H. Claas
- 6Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, Netherlands
- Henny G. Otten
- Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands
- DOI
- https://doi.org/10.3389/fimmu.2018.03002
- Journal volume & issue
-
Vol. 9
Abstract
The best treatment for patients with end-stage renal disease is kidney transplantation. Although graft survival rates have improved in the last decades, patients still may lose their grafts partly due to the detrimental effects of donor-specific antibodies (DSA) against human leukocyte antigens (HLA) and to a lesser extent also by antibodies directed against non-HLA antigens expressed on the donor endothelium. Assays to detect anti-HLA antibodies are already in use for many years and have been proven useful for transplant risk stratification. Currently, there is a need for assays to additionally detect multiple non-HLA antibodies simultaneously in order to study their clinical relevance in solid organ transplantation. This study describes the development, technical details and validation of a high-throughput multiplex assay for the detection of antibodies against 14 non-HLA antigens coupled directly to MagPlex microspheres or indirectly via a HaloTag. The non-HLA antigens have been selected based on a literature search in patients with kidney disease or following transplantation. Due to the flexibility of the assay, this approach can be used to include alternative antigens and can also be used for screening of other organ transplant recipients, such as heart and lung.
Keywords
