Tacrolimus CYP3A Single-Nucleotide Polymorphisms and Preformed T- and B-Cell Alloimmune Memory Improve Current Pretransplant Rejection-Risk Stratification in Kidney Transplantation
| Autor: | Elena Crespo, Anna Vidal-Alabró, Thomas Jouve, Pere Fontova, Maik Stein, Sonila Mocka, Maria Meneghini, Anett Sefrin, Petra Hruba, Montserrat Gomà, Alba Torija, Laura Donadeu, Alex Favà, Josep M. Cruzado, Edoardo Melilli, Francesc Moreso, Ondrej Viklicky, Frederike Bemelman, Petra Reinke, Josep Grinyó, Nuria Lloberas, Oriol Bestard |
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| Přispěvatelé: | Institut Català de la Salut, [Crespo E, Torija A, Donadeu L] Laboratori de Nefrologia i Trasplantament Renal, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. [Vidal-Alabró A, Fontova P, Mocka S] Experimental Nephrology and Transplantation Laboratory, Instituto de Investigación Biomédica de Bellvitge (IDIBELL), Barcelona, Spain. [Jouve T] Laboratori de Nefrologia i Trasplantament Renal, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. Faculty of Health, Université Grenoble Alpes, Grenoble, France. Institute for Advanced Biosciences, INSERM 1209, CNRS 5309, Grenoble, France. [Stein M] Berlin Center for Advanced Therapies (BeCAT), Berlin, Germany. Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany. Berlin Institute of Health (BIH), Berlin, Germany. [Meneghini M, Bestard O] Laboratori de Nefrologia i Trasplantament Renal, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. Unitat de Trasplantament Renal, Servei de Nefrologia, Vall d’Hebron Hospital, Barcelona, Spain. [Moreso F] Unitat de Trasplantament Renal, Servei de Nefrologia, Vall d’Hebron Hospital, Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus, Nephrology, AII - Inflammatory diseases, APH - Aging & Later Life |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
T-Lymphocytes
Immunology Trasplantament renal kidney transplantation Cèl·lules B - Immunologia Polymorphism Single Nucleotide Risk Assessment acute rejection Tacrolimus Kidney transplantation Cells::Antibody-Producing Cells::B-Lymphocytes [ANATOMY] fenómenos genéticos::variación genética::polimorfismo genético::polimorfismo de nucleótido único [FENÓMENOS Y PROCESOS] Memory B Cells Therapeutics::Renal Replacement Therapy::Kidney Transplantation [ANALYTICAL DIAGNOSTIC AND THERAPEUTIC TECHNIQUES AND EQUIPMENT] Immunology and Allergy Cytochrome P-450 CYP3A Humans calcineurin inhibitors immunosuppression genetics Immunologia immunobiology células::células productoras de anticuerpos::linfocitos B [ANATOMÍA] Genetic Phenomena::Genetic Variation::Polymorphism Genetic::Polymorphism Single Nucleotide [PHENOMENA AND PROCESSES] Polimorfisme genètic Ronyons - Trasplantació Immunosupressive agents terapéutica::tratamiento de reemplazo renal::trasplante de riñón [TÉCNICAS Y EQUIPOS ANALÍTICOS DIAGNÓSTICOS Y TERAPÉUTICOS] Immunosupressors |
| Zdroj: | Scientia Frontiers in immunology, 13:869554. Frontiers Media S.A. Dipòsit Digital de la UB Universidad de Barcelona |
| ISSN: | 1664-3224 |
| Popis: | Rechazo agudo; Genética; Inmunobiología Rebuig agut; Genètica; Immunobiologia Acute rejection; Genetics; Immunobiology Achieving fast immunosuppression blood exposure after kidney transplantation is key to abrogating both preformed and de novo anti-donor humoral and cellular alloresponses. However, while tacrolimus (TAC) is the cornerstone immunosuppressant inhibiting adaptive alloimmunity, its blood exposure is directly impacted by different single-nucleotide polymorphisms (SNPs) in CYP3A TAC-metabolizing enzymes. Here, we investigated how functional TAC-CYP3A genetic variants (CYP3A4*22/CYP3A5*3) influence the main baseline clinical and immunological risk factors of biopsy-proven acute rejection (BPAR) by means of preformed donor-specific antibodies (DSAs) and donor-specific alloreactive T cells (DSTs) in a large European cohort of 447 kidney transplants receiving TAC-based immunosuppression. A total of 70 (15.7%) patients developed BPAR. Preformed DSAs and DSTs were observed in 12 (2.7%) and 227 (50.8%) patients, respectively. According to the different CYP3A4*22 and CYP3A5*3 functional allele variants, we found 4 differential new clusters impacting fasting TAC exposure after transplantation; 7 (1.6%) were classified as high metabolizers 1 (HM1), 71 (15.9%) as HM2, 324 (72.5%) as intermediate (IM), and 45 (10.1%) as poor metabolizers (PM1). HM1/2 showed significantly lower TAC trough levels and higher dose requirements than IM and PM (p < 0.001) and more frequently showed TAC underexposure ( |
| Databáze: | OpenAIRE |
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