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

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-beta 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.