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Background: Biliary atresia (BA) is a type of severe cholestatic childhood disease that may have a genetic component. miR-100 plays a key role in regulating cell apoptosis, proliferation, and inflammatory reactions. A single-nucleotide polymorphism in miR-100 has been proven to modulate susceptibility to various diseases., Methods: We conducted a case-control retrospective study to explore the correlation between miR-100 gene polymorphism (rs1834306 A>G) and biliary atresia susceptibility in 484 Chinese patients and 1445 matched control subjects., Results: Our results showed that rs1834306 A>G was correlated with a significantly increased risk for BA (GG vs. AA: adjusted odds ratio (OR) = 1.44, 95%confidence interval (CI) = 1.02-2.03, p = 0.041; and GG vs. AA/AG: adjusted OR = 1.39, 95%CI = 1.02-1.89, p = 0.036)., Conclusions: Our results showed that the rs1834306 A>G polymorphism is associated with an increased risk for BA and contributes to BA susceptibility., Competing Interests: The authors declare that this research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jiaming Chang et al.)

Background & Aims: We have previously reported on the potential pathogenic role of neutrophils in biliary atresia (BA). Herein, we aimed to delineate the role of CD177+ neutrophils in the pathogenesis of BA., Methods: Immune cells from the livers of mice with rhesus rotavirus-induced BA were analysed. Single-cell RNA-sequencing was performed to specifically analyse Gr-1 + (Ly6C/Ly6G + ) cells in the liver. Gene expression profiles of CD177 + cells were analysed using the Smart-Seq RNA-sequencing method, and the pathogenesis of BA was examined in Cd177 -/- mice. Neutrophil extracellular trap (NET) inhibitors were used to determine the role of CD177 + cell-derived NETs in BA-associated bile duct damage, and a pilot clinical study evaluated the potential effects of N-acetylcysteine on NET release in BA., Results: Increased levels of Gr-1 + cells were observed in the livers of mice with rhesus rotavirus-induced BA. RNA-sequencing analysis revealed that CD177 + cells were the main population of Gr-1 + cells and expressed elevated levels of both interferon-stimulated and neutrophil degranulation genes. Cd177 -/- BALB/c mice exhibited delayed disease onset and reduced morbidity and mortality. High numbers of mitochondria were detected in CD177 + cells derived from mice with BA; these cells were associated with increased levels of reactive oxygen species and increased NET formation, which induced the apoptosis of biliary epithelial cells in cocultures. In a pilot clinical study, the administration of N-acetylcysteine to patients with BA reduced CD177 + cell numbers and reactive oxygen species levels, indicating a potential beneficial effect., Conclusions: Our data indicate that CD177 + cells play an important role in the initiation of BA pathogenesis via NET formation., Clinical Trial Registration: The pilot study of N-acetylcysteine treatment in patients with BA was registered on the Chinese Clinical Trial Registry (ChiCTR2000040505)., Lay Summary: Neutrophils (a type of innate immune cell, i.e. an immune cell that doesn't target a specific antigen) are thought to play a role in the development of biliary atresia (a rare but potentially lethal condition of the bile ducts that occurs in infants). Herein, we found that neutrophils expressing a particular protein (CD177) played an important role in bile duct damage by releasing a special structure (NET) that can trap and kill pathogens but that can also cause severe tissue damage. A pilot study in patients with biliary atresia showed that inhibiting NETs could have a beneficial effect., Competing Interests: Conflict of interest The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Correctly identifying patients with biliary atresia (BA), while avoiding invasive diagnostic methods is challenging. The purpose of this study was to determine the value of serum immune indicators for distinguishing BA from other causes of cholestasis in infants., Patients and Methods: The data of infants with a surgical/histological diagnosis of BA and those with other causes of cholestatic jaundice were retrospectively analyzed. Patients were divided into a BA group and a cholestasis control (CC) group. Biochemical parameters, major lymphocyte subsets, immunoglobin and C3 and C4 complement levels were compared between the groups., Results: A total of 129 infants with BA and 63 with other causes of cholestasis (CC control group) with a median age of 2.2 months were included in the analysis. The levels of CD3 + T cells, CD3 + CD4 + T cells, and premature T cells and the levels of C3 and C4 were all significantly higher in the BA group compared to the CC group (all P<0.05). Pair-wise correlation analyses indicated that C3 and C4 had a significant positive correlation with γ-GT in the BA group, but not in the CC group. Five indices were found to be significantly associated with BA: stool color, globulin, γ-GT, C3 and C4. A model incorporating stool color, gamma-glutamyl transpeptidase level, and C3 level exhibited an area under the ROC curve (AUC) of 0.93, and a sensitivity of 93% and specificity of 83% for the diagnosis of BA., Conclusions: Models incorporating serum C3 levels may be useful for accurately diagnosing BA in infants., (Copyright © 2021 Elsevier España, S.L.U. All rights reserved.)

Biliary atresia (BA) is a severe cholangiopathy that leads to liver failure in infants, but its pathogenesis remains to be fully characterized. By single-cell RNA profiling, we observed macrophage hypo-inflammation, Kupffer cell scavenger function defects, cytotoxic T cell expansion, and deficiency of CX3CR1 + effector T and natural killer (NK) cells in infants with BA. More importantly, we discovered that hepatic B cell lymphopoiesis did not cease after birth and that tolerance defects contributed to immunoglobulin G (IgG)-autoantibody accumulation in BA. In a rhesus-rotavirus induced BA model, depleting B cells or blocking antigen presentation ameliorated liver damage. In a pilot clinical study, we demonstrated that rituximab was effective in depleting hepatic B cells and restoring the functions of macrophages, Kupffer cells, and T cells to levels comparable to those of control subjects. In summary, our comprehensive immune profiling in infants with BA had educed that B-cell-modifying therapies may alleviate liver pathology., Competing Interests: Declaration of Interests The authors declare an application of patents describing diagnosis and treatment of BA., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Biliary atresia (BA) has complex genetic etiology, characterized by different levels of hepatic fibrosis after the Kasai procedure and immune responses to the bile duct. As an activator of the two most important inflammatory cells in Biliary atresia (T cells and NK cells), IL-18 is significantly increased in BA patients. This study aims to investigate the association of Interleukin 18(IL-18) with the susceptibility to BA. We examined the association of three polymorphisms (rs549908, rs187238 and rs1946518 in IL-18) and BA susceptibility in a Southern Chinese population composed of 506 cases and 1473 controls. SNP rs187238 and rs1946518 were identified as associated with BA. Interestingly, we also observed that the intragenic synergistic epistasis between SNPs rs187238 and rs1946518 boosting the risk to BA by logistic regression and Multifactor dimensionality reduction (MDR) analysis. This study provides for the first time a direct evidence to support IL-18 as a susceptibility gene for the disease in southern Chinese children., (Copyright © 2018 Elsevier B.V. All rights reserved.)