The Expression And Significance Of TGF-β1 And IL-17 In Autoimmune Liver Diseases

Objective To investigate and compare the clinicopathologic characteristics of patients with autoimmune hepatitis(AIH),primary biliary cirrhosis(PBC) and its overlap syndrome(AIH-PBC OS).To study the expression and significance of transforming growth factor-β1(TGF-β1 ),Interleukin-17(IL-17) in liver tissues of patients with AIH, PBC or AIH-PBC OS.Methods Forty-eight patients with autoimmune liver diseases(24 AIH,13 PBC and 11 AIH-PBC OS) were enrolled in the study,their clinical manifestations,serum liver function tests,serum immunoglobulins,liver histopathological changes were analyzed.Besides,their liver biopsy specimens were detected for TGF-β1 or IL-17 by immunohistochemical staining method.Results1.Most of the patients were female,they were always accompanied by other autoimmune diseases and diabetes.Moreover,some PBC and AIH-PBC OS patients suffered from hyperlipoidemia.The initial symptoms of AIH were manifestations of chronic liver diseases such as debility,fever,anorexia, abdominal discomfort and so on.while PBC were pruritus.2.Patients with AIH had significantly higher serum levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST) and immunoglobulin G(IgG) but lower serum levels of alkaline phosphatase(ALP),gamma -glutamyltransferase(GGT) and immunoglobulin M(IgM) than patients with PBC(P＜0.05).While patients with AIH-PBC OS had varying elevated serum levels of ALT,AST,ALP,GGT,IgG and IgM.3.More than 80%of the patients were antinuclear antibody(ANA) positive,while the vast majority of PBC and AIH-PBC OS patients were antimitochondrial antibody(AMA) positive.Besides,some AIH and AIH-PBC OS patients were positive for antismooth muscle antibody(SMA).4.The typical pathological features of AIH were interface hepatitis and rosette formation of liver cells(P＜0.05),while PBC were non-traumatic suppurative cholangitis and granulomatous cholangitis(P＜0.05).Besides,patients with AIH-PBC OS had pathological features of both AIH and PBC.5.Abdominal ultrasound showed that approximately 50%of the patients accompanied by celiac lymphadenectasis.Moreover,some PBC and AIH-PBC OS patients suffered from cholecystolithiasis.6.Non-parenchymal cells in portal tracts,fibrous septa and sinusoids showed strong expression of TGF-β1,which was significantly increased in liver tissues of patients with AIH,PBC or AIH-PBC OS,compared with control group(P＜0.05). No significant difference was observed among AIH,PBC or AIH-PBC OS.IL-17 staining was positive in the hepatic monocytes of AIH,PBC and AIH-PBC OS patients,especially portal tracts infiltrated with inflammatory cells.However,it was negative in the normal liver tissues.Conclusions1.AIH and PBC are representative autoimmune liver diseases in which hepatocytes and intrahepatic bile ducts,respectively,are selectively damaged by autoimmue mechanisms.The typical serological abnomal of AIH is hepatitis,while PBC is cholestasis.AIH-PBC OS has serological and histological characteristics of both PBC and AIH.2.TGF-β1 expression not only localizes in the inflammatory area,but also in fibrogenesis area shows that it is closely associated with hepatic inflammation and fibrogenesis of patients with autoimmune liver diseases.3.Our findings suggest that autoimmune liver diseases should be Th17-related autoimmune diseases.The over-expression of TGF-β1 may induce the differentiation of Th17 cells,further aggravate the hepatic inflammation.