Abstract
To investigate the immunopathogenic mechanisms of type I autoimmune hepatitis in children, we analyzed by quantitative or semiquantitative reverse transcription-polymerase chain reaction the expression of cytokines interferon (IFN)-gamma, interleukin (IL)-12p40, IL-18, IL-4, IL-10, and IL-12R beta 2. In addition, liver and peripheral blood was collected to investigate the expression of the natural killer T (NKT) cell marker V alpha 24. The presence of NKT cells in hepatic lesions were also identified by immunohistochemistry. The analysis was performed on liver biopsies from 25 children with type I autoimmune hepatitis. As disease controls, we included six children with hepatitis C virus-related chronic hepatitis and nine control livers. The expression of IFN-gamma and IL-12p40 was not detected in controls but was clearly upregulated in pathologic biopsies. In addition, these samples showed an increased expression of IL-18 (p = 0.0003), IL-4 (p = 0.0055), and IL-12R beta 2 (p = 0.007). Western blot analysis confirmed the expression of IL-12p40 and IL-18. However, for IL-18, we detected only the immature biologically inactive polypeptide. The V alpha 24 transcripts were found increased in the liver (p = 0.0007) where V alpha 24(+) cells were also localized, but decreased in peripheral blood mononuclear cells (p = 0.041). In addition to a type I immune response, NKT cells might play a substantial role in the pathogenesis of type I autoimmune hepatitis in children.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adolescent
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Autoantibodies / blood
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Biopsy, Needle
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Blood Chemical Analysis
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Blotting, Western
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Child
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Cytokines / genetics*
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Cytokines / immunology
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Cytokines / metabolism
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Female
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Gene Expression*
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Hepatitis, Autoimmune / genetics
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Hepatitis, Autoimmune / immunology
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Hepatitis, Autoimmune / pathology*
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Humans
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Immunohistochemistry
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Interferon-gamma / genetics
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Interleukin-10 / genetics
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Interleukin-10 / metabolism
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Interleukin-12 / genetics
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Interleukin-12 / metabolism
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Interleukin-12 Subunit p40
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Interleukin-18 / genetics
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Interleukin-18 / metabolism
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Interleukin-4 / genetics*
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Interleukin-4 / immunology
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Interleukin-4 / metabolism
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Killer Cells, Natural / immunology
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Killer Cells, Natural / metabolism
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Killer Cells, Natural / pathology
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Leukocytes, Mononuclear / chemistry
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Liver / immunology
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Liver / metabolism
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Liver / pathology
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Male
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Protein Subunits / genetics
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Protein Subunits / metabolism
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Receptors, Antigen, T-Cell, alpha-beta / analysis
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Receptors, Antigen, T-Cell, alpha-beta / genetics
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Receptors, Interleukin / genetics
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Receptors, Interleukin / metabolism
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Receptors, Interleukin-12
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T-Lymphocytes, Helper-Inducer / immunology
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T-Lymphocytes, Helper-Inducer / metabolism
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Th1 Cells / immunology*
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Th1 Cells / metabolism
Substances
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Autoantibodies
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Cytokines
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Interleukin-12 Subunit p40
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Interleukin-18
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Protein Subunits
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Receptors, Antigen, T-Cell, alpha-beta
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Receptors, Interleukin
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Receptors, Interleukin-12
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Interleukin-10
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Interleukin-12
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Interleukin-4
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Interferon-gamma