ArticleHepatology (Baltimore, Md.)2021
Unique Cholangiocyte-Targeted IgM Autoantibodies Correlate With Poor Outcome in Biliary Atresia.
Article in Hepatology (Baltimore, Md.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Biliary atresia.Nature reviews. Disease primers · 2024Review
- Proteomics Defines Plasma Biomarkers for the Early Diagnosis of Biliary Atresia.Journal of proteome research · 2024Article
- Single cell RNA-sequencing analysis reveals thatJHEP reports : innovation in hepatology · 2023Article
- Contribution ofInternational journal of molecular sciences · 2023Article
- The Role of Inflammation in Cholestatic Liver Injury.Journal of inflammation research · 2023Review
- A novel model based on immune-related genes for differentiating biliary atresia from other cholestatic diseases.Pediatric surgery international · 2022Article
- Diagnostic values of plasma matrix metalloproteinase-7, interleukin-8, and gamma-glutamyl transferase in biliary atresia.European journal of pediatrics · 2022Article
- Biliary Atresia in Children: Update on Disease Mechanism, Therapies, and Patient Outcomes.Clinics in liver disease · 2022Review
- Regulatory T Cell (Treg) Cytotoxic T Lymphocyte-associated Antigen-4 Deficits in Biliary Atresia (BA) and Disease Rescue With Treg Augmentation in Murine BA.Gastro hep advances · 2022Article
- Genetic Factors and Their Role in the Pathogenesis of Biliary Atresia.Frontiers in pediatrics · 2022Review
- Biliary Atresia - emerging diagnostic and therapy opportunities.EBioMedicine · 2021Review
- Altered T-Cell Receptor β-Chain and Lactate Dehydrogenase Are Associated With the Immune Pathogenesis of Biliary Atresia.Frontiers in medicine · 2021Article
- Discovery of Candidate Stool Biomarker Proteins for Biliary Atresia Using Proteome Analysis by Data-Independent Acquisition Mass Spectrometry.Proteomes · 2020Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
BACKGROUND AND
aimsThe etiology of biliary atresia (BA) is not known and is likely multifactorial, including a genetic predisposition, a viral or environmental trigger, an aberrant autoimmune response targeting cholangiocytes, and unique susceptibilities of the neonatal bile ducts to injury. Damaged cholangiocytes may express neo self-antigens and elicit autoreactive T-cell-mediated inflammation and B-cell production of autoantibodies. The aim of this study was to discover autoantibodies in BA that correlated with outcomes. APPROACH AND
resultsAn autoantigen microarray encompassing approximately 9,500 autoantigens was used to screen for serum immunoglobulin M (IgM) and immunoglobulin G (IgG) autoantibodies in patients with BA or other liver disease controls. Validation of candidate autoantibodies by enzyme-linked immunosorbent assay on a second cohort of subjects (6-12 months following Kasai portoenterostomy) and correlations of autoantibodies with outcomes were performed (serum bilirubin levels and need for liver transplant in first 2 years of life). Mean anti-chitinase 3-like 1 (CHI3L1), anti-delta-like ligand (DLL-4), and antisurfactant protein D (SFTPD) IgM autoantibodies in BA were significantly higher compared with controls, and IgM autoantibody levels positively correlated with worse outcomes. Immunofluorescence revealed cholangiocyte-predominant expression of CHI3L1, DLL-4, and SFTPD. The humoral autoantibody response was associated with C3d complement activation and T-cell autoimmunity, based on detection of cholangiocyte-predominant C3d co-staining and peripheral blood autoreactive T cells specific to CHI3L1, DLL-4 and SFTPD, respectively.
conclusionsBA is associated with cholangiocyte-predominant IgM autoantibodies in the first year after Kasai portoenterostomy. Anti-CHI3L1, anti-DLL-4, and anti-SFTPD IgM autoantibody correlations with worse outcomes and the detection of C3d on cholangioctyes and antigen-specific autoreactive T cells suggest that autoimmunity plays a role in the ongoing bile duct injury and progression of disease.
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