Increased serum GM-CSF at diagnosis of biliary atresia is associated with improved biliary drainage.

Abstract

Background: The immune heterogeneity of biliary atresia (BA) presents a challenge for development of prognostic biomarkers. This study aimed to identify early immune signatures associated with biliary drainage after Kasai Portoenterostomy (KPE).

Methods: Serum samples, liver slides, and clinical data were obtained from patients enrolled in the NIDDK-supported Childhood Liver Disease Research Network. Serum cytokines and hepatic immune cell subsets were measured at diagnosis and compared among 3 groups: 38 infants with BA (20 with evidence of bile flow after KPE; 18 without) and 17 non-BA cholestatic infants.

Results: BA participants had lower numbers of lipid associated macrophages (LAM), and increased serum levels of Eotaxin-3, interleukin (IL) 12p70, and IL-8 versus non-BA groups (p < 0.05 for all). Among BA participants, monocyte like macrophages and serum levels of granulocyte-macrophage colony stimulating factor (GM-CSF) were increased in BA participants with good biliary drainage (p = 0.004 and p < 0.001 respectively). Levels of GM-CSF, IL-16, c-reactive protein, TNF-β predicted successful biliary drainage with an area under the receiver operating curve of 0.84 (p < 0.001).

Conclusion: These findings suggest that distinct macrophage-associated immune networks at diagnosis may impact biliary drainage after KPE. Identification of early prognostic immune-modulatory markers has potential to improve patient stratification for medical and surgical therapies.

Impact statement: We identify serum cytokines, particularly GM-CSF, that are associated with future biliary drainage in patients with biliary atresia. Characterization of macrophage-associated immune networks provides novel insight into early disease mechanism that may impact patient outcomes. Early prognostic biomarkers markers in biliary atresia can help in patient stratification for medical and surgical therapies.