RNA-Sequencing Analysis Identifies Etiology Specific Transcriptional Signatures in Neonatal Acute Liver Failure - 15/03/23
Abstract |
Objective |
To assess hepatic transcriptional signatures in infants with gestational alloimmune liver disease (GALD) compared with other etiologies of neonatal acute liver failure (ALF) and older pediatric patients with ALF.
Study design |
Neonates with ALF (international normalized ratio ≥2 within 30 days of life) and deceased neonates without liver disease (<30 days of age) with available liver tissue between 2010 and 2021 were identified at Ann & Robert H. Lurie Children's Hospital of Chicago. Clinical information, liver histology, and data from RNA-sequencing analysis was compared between neonates with GALD, non-GALD etiologies of neonatal ALF, and nondiseased neonatal liver.
Results |
Quantification of trichrome staining showed an increase in fibrosis in patients with GALD vs those with non-GALD neonatal ALF (P = .012); however, quantification of α-cytokeratin 19–positive ductules did not differ between groups (P = .244). Gene set enrichment analysis of RNA-sequencing data identified the pathways of complement activation, fibrosis, and organogenesis to be upregulated in patients with GALD with ALF. In contrast, patients with non-GALD causes of neonatal ALF had increased gene expression for interferon-driven immune pathways. Individual genes upregulated in GALD included matrix metallopeptidase 7, hepatocyte growth factor, and chemokine ligand 14.
Conclusions |
We have identified distinct pathways that are significantly upregulated in patients with GALD and potential disease-specific diagnostic biomarkers. Future studies will aim to validate these findings and help identify GALD-specific diagnostic biomarkers to improve diagnostic accuracy and reduce GALD-associated patient mortality.
Le texte complet de cet article est disponible en PDF.Keywords : gestational alloimmune liver disease (GALD), pediatric acute liver failure, hepatic regeneration, liver fibrosis, ductular reaction
Abbreviations : ALF, CK19, CXCL14, DGE, FFPE, GALD, HGF, INR, IVIG, MMP7, NOTCH1, PALF, PCA, RNA-seq
Plan
| Supported by Northwestern Medicine Digestive Health Foundation (S.S., S.T.); National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases (1K08DK121937 to S.T.); Pediatric Liver Research Fund, Ann & Robert H. Lurie Children's Hospital Foundation (E.A., S.T.). This study was supported by clinical and research advancements in the field from Dr Peter Whitington and Susan Kelly, RN, as well as contributions from women and children affected by GALD, including the Pediatric Liver Research Fund and Ann & Robert H. Lurie Children's Hospital Foundation. The authors declare no conflicts of interest. |
Vol 253
P. 205 - février 2023 Retour au numéro
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