The molecular diagnosis of rejection in liver transplant biopsies: First results of the INTERLIVER study
| Autor: | Rosa Miquel, Chandra Bhati, Katelynn S. Madill-Thomsen, Goran B. Klintmalm, Olga Tronina, Maciej Krasnodębski, Krzysztof Zieniewicz, Leszek Pączek, Marta Wawrzynowicz-Syczewska, Grzegorz Piecha, Andrzej Wiecek, Michał Grąt, Trevor Reichman, Marwan S Abouljoud, Sandy Feng, Iman Francis, Geoff McCaughan, Michał Ciszek, Agnieszka Perkowska-Ptasińska, Dilip Moonka, Bartosz Foroncewicz, Philip F. Halloran, Krzysztof Jurczyk, Krzysztof Mucha, Alberto Sanchez-Fueyo, Marek Myślak, Aldo J. Montano-Loza, Magdalena Durlik |
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| Rok vydání: | 2020 |
| Předmět: |
Pathology
medicine.medical_specialty Population 030230 surgery 03 medical and health sciences 0302 clinical medicine Fibrosis Biopsy medicine Immunology and Allergy Pharmacology (medical) education Transplantation Kidney education.field_of_study Lung biology medicine.diagnostic_test business.industry Histology medicine.disease medicine.anatomical_structure biology.protein Liver function Antibody business |
| Zdroj: | American Journal of Transplantation. 20:2156-2172 |
| ISSN: | 1600-6135 |
| Popis: | Molecular diagnosis of rejection is emerging in kidney, heart, and lung transplant biopsies and could offer insights for liver transplant biopsies. We measured gene expression by microarrays in 235 liver transplant biopsies from 10 centers. Unsupervised archetypal analysis based on expression of previously annotated rejection-related transcripts identified 4 groups: normal "R1normal " (N = 129), T cell-mediated rejection (TCMR) "R2TCMR " (N = 37), early injury "R3injury " (N = 61), and fibrosis "R4late " (N = 8). Groups differed in median time posttransplant, for example, R3injury 99 days vs R4late 3117 days. R2TCMR biopsies expressed typical TCMR-related transcripts, for example, intense IFNG-induced effects. R3injury displayed increased expression of parenchymal injury transcripts (eg, hypoxia-inducible factor EGLN1). R4late biopsies showed immunoglobulin transcripts and injury-related transcripts. R2TCMR correlated with histologic rejection although with many discrepancies, and R4late with fibrosis. R2TCMR , R3injury , and R4late correlated with liver function abnormalities. Supervised classifiers trained on histologic rejection showed less agreement with histology than unsupervised R2TCMR scores. No confirmed cases of clinical antibody-mediated rejection (ABMR) were present in the population, and strategies that previously revealed ABMR in kidney and heart transplants failed to reveal a liver ABMR phenotype. In conclusion, molecular analysis of liver transplant biopsies detects rejection, has the potential to resolve ambiguities, and could assist with immunosuppressive management. |
| Databáze: | OpenAIRE |
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