A project of the Medical University of Vienna supported by the Wiener Wissenschafts-, Forschungs und Technologiefonds (LS20-081)
In our previous WWTF funded research (Polimorph) we showed that non-HLA genetic mismatch in kidney transplant donor and recipient pairs have a major impact on graft survival (Reindl-Schwaighofer et al. Lancet 2019). This data extended the concept of HLA epitope mismatch to genome-wide incompatibilities. The applied genotyping approach allowed for the simultaneous evaluation of over 50,000 genetic variants that result in amino acid mismatches and reflected genetic variation on the population level. Not all identified variants were immunogenic and resulted in antibody formation. Following up on this data we propose a refined risk prediction tool based on: a) whole exome sequencing in 350 transplant pairs from our prospective transplant biobank to cover individual level genetic variation that can not be identified using genotyping and b) a refined bioinformatics pipeline to identify immunogenic variants by integrating antibody accessibility (protein structure) and indirect allorecognition by recipient T-cells (MHC-restriction). As a proof of principle, the detection of antigen-specific indirectly alloreactive T-cells will be tested by using HLA class II / allopeptide tetramers to provide novel insight into the immunogenicity of HLA and non-HLA incompatibilities on a mechanistic level. Overall this research will increase our understanding of immunological non-self and ultimately make immunological risk stratification clinically feasible and thus allow for a personalized medicine approach.
GenTx is a multi-year research project funded by the Vienna Science and Technology Fund (WWTF - LS20-081). It has started in 2021.
More about WWTF.In unserem letzten WWTF-geförderten Projekt konnten wir zeigen, dass genetische Unterschiede zwischen Spendern und Empfängern bei Nierentransplantation einen großen Einfluss auf das Überleben der Organe haben (Reindl-Schwaighofer et al. Lancet 2019). Diese Ergebnisse erweiterten das Konzept des immunologischen "selbst" bei Organtransplantation, welches nun Varianten, die über das gesamte Genom verteilt sind, umfasst. In einem nächsten Schritt sollen im aktuellen Projekt auch seltene genetische Varianten, die nur bei einzelnen Individuen vorkommen, durch Sequenzierung des Erbguts erkannt werden. Nicht alle Varianten führen aber zu einem gleich großen Effekt auf das Immunsystem, weshalb zusätzlich eine verbesserte Charakterisierung der Inkompatibilitäten erfolgen muss: Hier werden wir speziell darauf eingehen ob einzelne Varianten durch Antikörper erreicht bzw. durch das Immunsystem des Empfängers überhaupt erkannt werden können. Darüber hinaus soll eine Immunantwort gegen diese Varianten nachgewiesen werden, wobei wir sowohl Antikörpern als auch Immunzellen untersuchen werden. Insgesamt erlauben die durch diese Studie gewonnen Daten eine individualisierte Risikoabschätzung vor einer Nierentransplantation und wird eine individualisierte Therapie ermöglichen.
Rainer Oberbauer is a senior scientist in the field of transplantation and was the principal investigator of the previous WWTF funded research project (Polimorph). He has a long-standing track record in biomarker development using OMICS data as well as genetics in transplantation. He will coordinate and supervise the research efforts of this follow-up project.
Roman Reindl-Schwaighofer was the leading scientist in the previous research efforts on genome-wide incompatibility in transplantation (Polimorph) and has conceptualized the current proposal together with Rainer Oberbauer. He is in charge of the prospective Vienna transplant cohort and biobanking efforts and responsible for the implementation of the bioinformatics workflow in the POLiMORPH project. He will oversee and coordinate the WES and the implementation of the enhanced bioinformatics workflow for improved risk prediction based on donor recipient genetic mismatch.
Nikolina Papac-Milicevic is a young scientist and was also involved in the Polimorph project and is a postdoctoral fellow in the Daniela Pollak resarch group. She has a great experience in immunology and will oversee the wet-lab experiments including antibody testing and tetramer-staining.
Upcoming: 2025, Jun 29- Jul 02:
Meet us at the ESOT Congress in London, England
Programm
Upcoming: 2025, Jun 04-07:
Meet us at the 62nd ERA Congress in Vienna, Austria
Programm
2024, Aug 31:
Meet us at the 10th Living Donor Abdominal Organ Transplantation Conference in Rome,Italy
Transplant Nephrology Program: Are Immunorecognizable nonHLA epitopes important?
Programm
2024, Feb 26:
Meet us at the 16th East-West Immunogetics Conference in Vienna, Austria
Organ Transplantation: Non-HLA alloimmunity
Programm
2023, Jul 12:
Meet us at The Retreat of the Research Platform Transplantation of the Medical University of Vienna in Lower Austria, Austria
Keynote Lecture 5: Non-HLA immunity
Programm
2023, Jan 24:
Meet us at the 253. Nephrologisches Forum in Munich, Germany
Nierentransplantation - Bedeutung der Non-HLA Immunität
Programm
2022, Jun 17:
Meet us at the 10th Living Donor Abdominal Organ Transplantation Conference in Perugia,Italy
Living Donor Kidney Transplantation: nonHLA Alloimmunity
Programm
2021, Dec 10:
Meet us at the Congress of the Francophone Society of Transplantation in
Immunology and Transplantation - nonHLA alloimmunity in kidney transplantation
Programm
2021, Jun 08:
Meet us at the 58th ERA-EDTA Congress 2021 in Berlin, Germany
NON-HLA Incompatibilities: what´s new
Programm
Genome-wide donor recipient non-HLA mismatch and graft loss
Pickl J, Heinzel A, Shoebridge S, Kainz A, Oberbauer R
Nephrol Dial Transplant. 2025 Apr 25:gfaf073. doi: 10.1093/ndt/gfaf073
Link to publicaton
Polygenic risk scores in kidney transplantation
Jelencsics K, Oberbauer R
Curr Opin Organ Transplant. 2025 Apr 2. doi: 10.1097/MOT.0000000000001212
Link to publicaton
Association of Podometrics Findings in Patients With Hypertension and Type 2 Diabetes: A Retrospective Analysis
Paschen C, Koeller MC, Schachner H, Nackenhorst M, Kläger J, Oszwald A, Dörr K, Kammer M, Kozakowski N, Rees A, Kain R, Hecking M, Oberbauer R, Regele H
Hypertension. 2025 Mar 6. doi: 10.1161/HYPERTENSIONAHA.124.24379
Link to publicaton
The complement system in lipid-mediated pathologies
Alic L, Dendinovic K, Papac-Milicevic N
Front Immunol. 2024 Nov 20;15:1511886. doi: 10.3389/fimmu.2024.1511886
Link to publicaton
Combination cell therapy leads to clonal deletion of donor-specific T cells in kidney transplant recipients
David AF, Heinzel A, Kammer M, Aschauer C, Reindl-Schwaighofer R, Hu K, Chen HS, Muckenhuber M, Kubetz A, Weijler AM, Worel N, Edinger M, Berlakovich G, Lion T, Sykes M, Wekerle T, Oberbauer R
EBioMedicine. 2024 Aug;106:105239. doi: 10.1016/j.ebiom.2024.105239
Link to publication
Early progression of chronic histologic lesions in kidney transplant biopsies is not associated with HLA histocompatibility
Jabbour R, Heinzel A, Reindl-Schwaighofer R, Gregorich MG, Regele H, Kozakowski N, Kläger J, Fischer G, Kainz A, Becker JU, Wiebe C, Oberbauer R
Nephrol Dial Transplant. 2024 Apr 26;39(5):808-817. doi: 10.1093/ndt/gfad246
Link to publication
A pan-tissue survey of mosaic chromosomal alterations in 948 individuals
Gao T, Kastriti ME, Ljungström V, Heinzel A, Tischler AS, Oberbauer R, Loh PR, Adameyko I, Park PJ, Kharchenko PV
Nat Genet. 2023 Nov;55(11):1901-1911. doi: 10.1038/s41588-023-01537-1
Link to publication
Prospective assessment of pre-existing and de novo anti-HLA IgE in kidney, liver, lung and heart transplantation
Mucha J, Cho A, Weijler AM, Muckenhuber M, Hofmann AG, Wahrmann M, Heinzel A, Linhart B, Gattinger P, Valenta R, Berlakovich G, Zuckermann A, Jaksch P, Oberbauer R, Wekerle T
Front Immunol. 2023 Sep 5;14:1179036. doi: 10.3389/fimmu.2023.1179036
Link to publication
Effects of Reduced-Dose Anti-Human T-Lymphocyte Globulin on Overall and Donor-Specific T-Cell Repertoire Reconstitution in Sensitized Kidney Transplant Recipients
Aschauer C, Jelencsics K, Hu K, Gregorich M, Reindl-Schwaighofer R, Wenda S, Wekerle T, Heinzel A, Oberbauer R
Front Immunol. 2022 Feb 25;13:843452. doi: 10.3389/fimmu.2022.843452
Link to publication
The OSE complotype and its clinical potential
Alic L, Binder CJ, Papac-Milicevic N
Front Immunol. 2022 Sep 30;13:1010893. doi: 10.3389/fimmu.2022.1010893
Link to publication
Novel insights into Non-HLA Alloimmunity in Kidney Transplantation
Reindl-Schwaighofer R, Heinzel A, Gualdoni GA, Mesnard L, Claas FHJ, Oberbauer R
Transpl Int. 2020 Jan;33(1):5-17. doi: 10.1111/tri.13546
Link to pubication
Contribution of non-HLA incompatibility between donor and recipient to kidney allograft survival: genome-wide analysis in a prospective cohort
Reindl-Schwaighofer R, Heinzel A, Kainz A, van Setten J, Jelencsics K, Hu K, Loza BL, Kammer M, Heinze G, Hruba P, Koňaříková A, Viklicky O, Boehmig GA, Eskandary F, Fischer G, Claas F, Tan JC, Albert TJ, Patel J, Keating B, Oberbauer R; iGeneTRAiN consortium
Lancet. 2019 Mar 2;393(10174):910-917. doi: 10.1016/S0140-6736(18)32473-5
Link to publication
Strategies for Long-Term Preservation of Kidney Graft Function
Wekerle T, Segev D, Lechler R, Oberbauer R
Lancet. 2017 May 27;389(10084):2152-2162. doi: 10.1016/S0140-6736(17)31283-7
Link to pubication
Immune Repertoire Profiling Reveals that Clonally Expanded B and T Cells Infiltrating Diseased Human Kidneys Can Also Be Tracked in Blood
Weinberger J, Jimenez-Heredia R, Schaller S, Suessner S, Sunzenauer J, Reindl-Schwaighofer R, Weiss R, Winkler S, Gabriel C, Danzer M, Oberbauer R
PLoS One. 2015 Nov 23;10(11):e0143125. doi: 10.1371/journal.pone.0143125
Link to pubication
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