Simultaneous expression of Th1 cytokines and IL-4 confers severe characteristics to type I autoimmune hepatitis in children.
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.
División Inmunogenética, Hospital de Clínicas José de San Martín, Universidad de Buenos Aires, Av. Córdoba 2351 (1120) Buenos Aires, Argentina.
Alejandra Claudia
AC
Cherñavsky
Natalia
N
Paladino
Andrea Elena
AE
Rubio
María Bárbara
MB
De Biasio
Natalia
N
Periolo
Miriam
M
Cuarterolo
Javier
J
Goñi
Cristina
C
Galoppo
María Cristina
MC
Cañero-Velasco
Alberto Eduardo
AE
Muñoz
Hugo
H
Fainboim
Leonardo
L
Fainboim
D000293:Adolescent; D001323:Autoantibodies / Q000097:blood; D001707:Biopsy, Needle; D001774:Blood Chemical Analysis; D015153:Blotting, Western; D002648:Child; D016207:Cytokines / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D019693:Hepatitis, Autoimmune / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D018664:Interleukin-12 / Q000235:genetics / Q000378:metabolism; D053762:Interleukin-12 Subunit p40; D020382:Interleukin-18 / Q000235:genetics / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000737:chemistry; D008099:Liver / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis / Q000235:genetics; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism; D053707:Receptors, Interleukin-12; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism
D001323:Autoantibodies; D016207:Cytokines; D053762:Interleukin-12 Subunit p40; D020382:Interleukin-18; D021122:Protein Subunits; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma