Science and Research

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

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.

  • Kamp, J. C.
  • Madadi-Sanjani, O.
  • Uecker, M.
  • Werlein, C.
  • Neubert, L.
  • Kübler, J. F.
  • Obed, M.
  • Junge, N.
  • Welte, T.
  • Ruwisch, J.
  • Jonigk, D. D.
  • Stolk, J.
  • Vieten, G.
  • Janciauskiene, S.
Publication details
DOI: 10.1038/s41390-024-03582-w
Journal: Pediatr Res
Work Type: Original
Location: BREATH
Disease Area: ROR
Partner / Member: MHH
Access-Number: 39341941

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