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Sep 28, 2024;

Amyloid precursor protein as a fibrosis marker in infants with biliary atresia.

Jan C Kamp, Omid Madadi-Sanjani, Marie Uecker, Christopher Werlein, Lavinia Neubert, Joachim F Kübler, Mikal Obed, Norman Junge, Tobias Welte, Jannik Ruwisch, Danny D Jonigk, Jan Stolk, Gertrud Vieten, Sabina Janciauskiene
Author Information
  1. Jan C Kamp: Department of Respiratory and Infectious Medicine, Hannover Medical School, Hannover, Germany. Kamp.Jan-Christopher@mh-hannover.de. ORCID
  2. Omid Madadi-Sanjani: Centre of Pediatric Surgery, Hannover Medical School, Hannover, Germany.
  3. Marie Uecker: Centre of Pediatric Surgery, Hannover Medical School, Hannover, Germany.
  4. Christopher Werlein: Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), Hannover, Germany.
  5. Lavinia Neubert: Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), Hannover, Germany.
  6. Joachim F Kübler: Centre of Pediatric Surgery, Hannover Medical School, Hannover, Germany.
  7. Mikal Obed: Centre of Pediatric Surgery, Hannover Medical School, Hannover, Germany.
  8. Norman Junge: Division for Pediatric Gastroenterology and Hepatology, Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Hannover, Germany.
  9. Tobias Welte: Department of Respiratory and Infectious Medicine, Hannover Medical School, Hannover, Germany.
  10. Jannik Ruwisch: Department of Respiratory and Infectious Medicine, Hannover Medical School, Hannover, Germany.
  11. Danny D Jonigk: Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), Hannover, Germany.
  12. Jan Stolk: Department of Pulmonology, Leiden University Medical Center, Member of European Reference Network Lung, Section Alpha-1-Antitrypsin Deficiency, Leiden, The Netherlands.
  13. Gertrud Vieten: Centre of Pediatric Surgery, Hannover Medical School, Hannover, Germany.
  14. Sabina Janciauskiene: Department of Respiratory and Infectious Medicine, Hannover Medical School, Hannover, Germany.
PMID: 39341941 DOI: 10.1038/s41390-024-03582-w

Abstract

BACKGROUND: Biliary atresia (BA) is a rare condition of unknown origin in newborns with jaundice. In BA bile ducts are non-functional, causing neonatal cholestasis and following liver fibrosis and failure.
METHODS: This retrospective study included liver biopsies of 14 infants with BA aged [mean ± SD] 63 ± 23 days. Patients were grouped according to the clinical course (jaundice-free vs recurrent jaundice vs required liver transplantation or liver fibrosis (Ishak fibrosis score)) and followed for 1.61-5.64 years (mean 4.03). Transcriptome profiles were assessed using a panel of 768 fibrosis-specific genes, reanalyzed via qRT-PCR, and confirmed via immunostaining. Plasma from an additional 30 BA infants and 10 age-matched controls were used for amyloid precursor protein (APP) quantification by ELISA.
RESULTS: Different clinical outcome groups showed a homogeneous mRNA expression. Altered amyloid-metabolism-related gene expression was found between cases with Ishak fibrosis score greater than 4. Immunostaining confirmed a distinct presence of APP in the livers of all BA subjects. APP plasma levels were higher in BA than in age-matched controls and correlated with the histological fibrosis grade.
CONCLUSIONS: These results suggest that amyloidosis may contribute to BA and liver fibrosis, indicating that APP could serve as a potential liquid biomarker for these conditions.
IMPACT: Biliary atresia patients with higher fibrosis scores according to Ishak have higher hepatic expression of amyloid-related genes while amyloid precursor protein accumulates in the liver and increases in the circulation. After a recent study revealed beta-amyloid deposition as a mechanism potentially involved in biliary atresia, we were able to correlate amyloid-metabolism-related transcript levels as well as amyloid precursor protein tissue and plasma levels with the degree of hepatic fibrosis. These findings suggest that amyloid precursor protein is a fibrosis marker in infants with biliary atresia, reinforcing the role of amyloid metabolism in the pathogenesis of this serious disease.

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Journal Article

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