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  • Clinical Research Article
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Increased serum GM-CSF at diagnosis of biliary atresia is associated with improved biliary drainage

Pediatric Research (2025)Cite this article

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.

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Fig. 1: Increased hepatic MLM at baseline are present in BA patients with improved biliary drainage.
Fig. 2: Numbers of hepatic LAM at baseline are associated with higher 3-month TB levels and degree of fibrosis in BA.
Fig. 3: GM-CSF cytokine network at diagnosis is associated with biliary drainage at 3-months post-KPE.

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Data availability

The datasets generated during and/or analyzed during the current study are not publicly available but are available from the corresponding author on reasonable request.

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Acknowledgements

The authors acknowledge the support provided by the Northwestern University Pathology Core and Immunotherapy Assessment Core. Heather Van Doren, Senior Medical Editor with Arbor Research Collaborative for Health, provided editorial assistance on this manuscript.

Funding

Supported by the National Institute of Diabetes, Digestive, and Kidney Diseases (NIDDK) U01 grants (DK103149 to Baylor College of Medicine, DK062470 to Children’s Healthcare of Atlanta, DK103135 to The Hospital for Sick Children, DK062436 and DK062436-19S1 to Ann & Robert H. Lurie Children’s Hospital of Chicago, DK062497 to Cincinnati Children’s Hospital Medical Center, DK103140 to University of Utah, DK084575 to Seattle Children’s Hospital, DK062481 to The Children’s Hospital of Philadelphia, DK062466 to Children’s Hospital of Pittsburgh of the University of Pittsburgh Medical Center, DK062456 to University of Michigan, DK084536 to Riley Hospital for Children, DK062500 to University of California San Francisco Children’s Hospital, DK084538 to Children’s Hospital Los Angeles, DK062453 to University of Colorado Denver and Children’s Hospital Colorado) and the National Institutes of Health (NIH) National Center for Advancing Translational Sciences (NCATS), Clinical and Translational Sciences Awards (UL1TR002378 to Children’s Healthcare of Atlanta, UL1 TR000423 and UL1 RR025014 to Seattle Children’s Hospital, UL1 TR001878 to The Children’s Hospital of Philadelphia, UL1 TR001857 to Children’s Hospital of Pittsburgh of UPMC, UL1 TR001872 to UCSF Children’s Hospital, UL1 TR002535 and UM1 TR004399 to University of Colorado Denver, and UL1TR00130 to Children’s Hospital of Los Angeles). Additional support provided by NIDDK K08 grant DK121937 and R03 grant DK135784 (Sarah A. Taylor).

Author information

Authors and Affiliations

  1. Department of Pediatrics, Children’s Hospital Colorado and University of Colorado School of Medicine, Aurora, CO, USA

    Sarah A. Taylor & Ronald J. Sokol

  2. Department of Pediatrics, Texas Children’s Hospital, Houston, TX, USA

    Sanjiv Harpavat

  3. Department of Pediatrics, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, USA

    Kyle D. Gromer & Estella M. Alonso

  4. Arbor Research Collaborative for Health, Ann Arbor, MI, USA

    Victor Andreev

  5. Department of Pediatrics, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Kathleen M. Loomes

  6. Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Jorge A. Bezerra

  7. Department of Pediatrics, UT Southwestern Medical Center, Dallas, TX, USA

    Jorge A. Bezerra

  8. Department of Pediatrics, Riley Hospital for Children, Indianapolis, IN, USA

    Chaowapong Jarasvaraparn

  9. Department of Surgery, Children’s Hospital Los Angeles, Los Angeles, CA, USA

    Kasper Wang

  10. The Hospital for Sick Children, Toronto, Ontario, CA, USA

    Kasper Wang & Vicky L. Ng

  11. Department of Pediatrics, Children’s Hospital of Pittsburgh, Pittsburgh, PA, USA

    Simon Horslen

  12. Department of Pediatrics and Surgery, University of California San Francisco, San Francisco, CA, USA

    Philip Rosenthal

  13. Department of Pediatrics, Saint Louis University School of Medicine, SSM Health Cardinal Glennon Children’s Hospital, St. Louis, MO, USA

    Jeffrey Teckman

  14. Department of Pediatrics, Seattle Children’s Hospital, Seattle, WA, USA

    Pamela L. Valentino

  15. Department of Pediatrics, Children’s Healthcare of Atlanta, Atlanta, GA, USA

    Saul J. Karpen

  16. Department of Pediatrics, Virginia Commonwealth University, Richmond, VA, USA

    Saul J. Karpen

  17. Department of Pediatrics, Medical College of Wisconsin, Children’s Wisconsin, Milwaukee, WI, USA

    Cara L. Mack

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  1. Sarah A. Taylor
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Consortia

for the Childhood Liver Disease Research Network (ChiLDReN)

Contributions

Substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data was made by SAT, SH, KDG, SJK, RJS, EMA, and CLM. Drafting the article or revising it critically for important intellectual content was performed by SAT, SH, KML, JAB, CJ, PLV, RJS, EMA, and CLM. Final approval of the version to be published was completed by all authors: SAT, SH, KDG, VA, KML, JAB, CJ, KW, SH, PR, JT, PLV, VLN, SJK, RJS, EMA, and CLM.

Corresponding author

Correspondence to Sarah A. Taylor.

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Competing interests

SAT serves as a consultant for Ipsen and Mirum Pharma. SH serves on the Data Safety Monitoring Board coordinated by Syneos Health for a therapeutic drug trial for biliary atresia. KML serves as a consultant for Ipsen and Mirum Pharma. PV serves on the Speaker’s Bureau for Mirum and is a consultant for Grifols. SJK serves as a consultant for Ipsen, Hemoshear, Intercept, Mirum, and Vertex. RJS serves as consultant for Ipsen and Mirum Pharma. All remaining coauthors declare no conflicts of interest for this manuscript.

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Written informed consent was obtained for all participants. Institutional review board approval was obtained for the study and conformed to the ethical guidelines of the 1975 Declaration of Helsinki.

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Taylor, S.A., Harpavat, S., Gromer, K.D. et al. Increased serum GM-CSF at diagnosis of biliary atresia is associated with improved biliary drainage. Pediatr Res (2025). https://doi.org/10.1038/s41390-025-03804-9

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  • DOI: https://doi.org/10.1038/s41390-025-03804-9

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