Chronic Antibody-Mediated Rejection in Nonhuman Primate Renal Allografts: Validation of Human Histological and Molecular Phenotypes.
Am J Transplant
; 17(11): 2841-2850, 2017 Nov.
Article
em En
| MEDLINE
| ID: mdl-28444814
ABSTRACT
Molecular testing represents a promising adjunct for the diagnosis of antibody-mediated rejection (AMR). Here, we apply a novel gene expression platform in sequential formalin-fixed paraffin-embedded samples from nonhuman primate (NHP) renal transplants. We analyzed 34 previously described gene transcripts related to AMR in humans in 197 archival NHP samples, including 102 from recipients that developed chronic AMR, 80 from recipients without AMR, and 15 normal native nephrectomies. Three endothelial genes (VWF, DARC, and CAV1), derived from 10-fold cross-validation receiver operating characteristic curve analysis, demonstrated excellent discrimination between AMR and non-AMR samples (area under the curve = 0.92). This three-gene set correlated with classic features of AMR, including glomerulitis, capillaritis, glomerulopathy, C4d deposition, and DSAs (r = 0.39-0.63, p < 0.001). Principal component analysis confirmed the association between three-gene set expression and AMR and highlighted the ambiguity of v lesions and ptc lesions between AMR and T cell-mediated rejection (TCMR). Elevated three-gene set expression corresponded with the development of immunopathological evidence of rejection and often preceded it. Many recipients demonstrated mixed AMR and TCMR, suggesting that this represents the natural pattern of rejection. These data provide NHP animal model validation of recent updates to the Banff classification including the assessment of molecular markers for diagnosing AMR.
Palavras-chave
animal models: nonhuman primate; basic (laboratory) research/science; classification systems: Banff classification; kidney (allograft) function/dysfunction; kidney transplantation/nephrology; molecular biology; molecular biology: mRNA/mRNA expression; pathology/histopathology; rejection: antibody-mediated (ABMR); translational research/science
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Transplante de Rim
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Rejeição de Enxerto
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Sobrevivência de Enxerto
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Isoanticorpos
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article