Abstract
Background: Biliary atresia (BA) is one of the most common and fatal abnormalities of newborns. Increasing evidences indicated that immunology was the critical part of the etiology. This research used a public gene expression database to explore the immune microenvironment of BA liver.Methods: The gene expression profiles GSE46960, GSE159720, and GSE15235, containing BA and normal liver gene expression data, were obtained from the Expression Omnibus Gene. We applied CIBERSORTx to quantify 22 subsets of immune cells in BA liver. The differentially expressed genes (DEGs) and immune cells were used to further explore their relationship with liver fibrosis and the inflammation status of BA.Results: The expression of immune-related genes CXCL6, CXCL8, CXCL10, CCL20, IL32, TGFB2, SPP1, and SLIT2 was significantly different between BA and normal liver, among which CXCL8 was the hub gene. Six of 22 immune cell proportions were significantly different between BA and normal liver. Specifically, M0 macrophages and resting memory CD4+ T cells were upregulated in BA liver compared with normal liver. Meanwhile, monocytes, resting natural killer (NK) cells, plasma cells, and regulatory T (Treg) cells were downregulated. A further correlation analysis revealed that SLIT2 and CXCL6 owned high positive correlation coefficients with fibrosis grade, while the proportion of resting NK cells was negatively correlated. Proportions of resting CD4+ memory T cells were strongly related to the inflammation grade of BA liver.Conclusion: Biliary atresia is a disease strongly correlated with immune response. Our results might provide a clue for further exploration of BA etiology, which may promote a potential prediction model based on immune infiltration features.
Highlights
IntroductionMost Biliary atresia (BA) patients cannot survive with their native liver because of severe cholestatic cirrhosis, unless they receive Kasai portoenterostomy to reconstruct the bile drainage [1]
Biliary atresia (BA) is one of the most common and fatal abnormalities of newborns
Eight of the 128 duplicated genes were found in ImmPort, suggesting that these differentially expressed genes (DEGs) were related to the immune process of BA (Figure 1A)
Summary
Most BA patients cannot survive with their native liver because of severe cholestatic cirrhosis, unless they receive Kasai portoenterostomy to reconstruct the bile drainage [1]. More than half of the patients cannot survive with their native liver for a long term after receiving Kasai portoenterostomy, which contributes to 75% of pediatric liver transplantation under 2 years old in the world [2]. Increasing evidence indicated that immunologic derangement was the core issue that caused BA. The abnormality of B cells, T cells, and macrophages in BA patients was revealed by single-cell RNA-seq in a small population recently, which provided strong evidence that the immune system took part in the occurrence and development of BA to a great extent [7]. Increasing evidences indicated that immunology was the critical part of the etiology. This research used a public gene expression database to explore the immune microenvironment of BA liver
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