Background: The diagnosis of drug-induced autoimmune hepatitis(DIAIH) and its differentiation from idiopathic autoimmune hepatitis(AIH) is challenging. This study aimed to differentiate DIAIH from AIH by comparing the biochemical changes, histological features, and frequencies of CD4^+Foxp3^+CD25^(+/-)regulatory T cells(Tregs) in liver tissues or peripheral blood lymphocytes.Methods: A total of 15 DIAIH patients and 24 AIH patients who underwent liver biopsies at initial presentation were enrolled in this study. The liver histological changes were assessed by HE staining. The phenotypic recognition and distribution of CD4^+Foxp3^+CD25^(+/-)Tregs in liver tissues were evaluated by single/double immunostains in serial sections. The CD4^+Foxp3^+CD25^(+/-)Tregs in peripheral blood were analyzed by flow cytometry.Results: The median values of ALT and AST were 404.50 U/L and 454.10 U/L in DIAIH patients and309.50 U/L and 315.00 U/L in AIH patients, respectively. More importantly, for the first time we found that patients with DIAIH had higher levels of serum ALT and AST, more severe degree of lobular inflammation,higher frequencies of zone 3 necrosis and higher number of lobular CD4^+Foxp3^+CD25^-Tregs compared with AIH(P < 0.05). Furthermore, there were positive correlations in DIAIH between the degree of lobular inflammation and either the AST/ALT level or the number of lobular CD4^+Foxp3^+CD25^-Tregs(P < 0.05).However, the frequency of peripheral blood CD4^+Foxp3^+CD25^(+/-)Tregs were not significantly different between DIAIH and AIH.Conclusions: The differences of ALT, AST and the number of lobular CD4^+Foxp3^+CD25^-Tregs between patients with DIAIH and those with AIH are clinically helpful in differentiating these two diseases in their early stage.
To the Editor:IgG4-related sclerosing cholangitis (IgG4-SC) has recently been recognized as a biliary manifestation of IgG4-related disease (IgG4-RD). Type 3 IgG4-SC presented biliary strictures in both the porta hepatis and the distal common bile duct (CBD).[1, 2] Its manifestation,especially in the absence of autoimmune pancreatitis, is extremely rare and very similar to that of cholangiocarcinoma(CC).Chronic sclerosing sialadenitis (Küttner tumor, KT)is an uncommon benign tumor-like lesion that most often affects the unilateral or bilateral submandibular glands.[3, 4] Recently, KT has been recognized within the spectrum of IgG4-RD.[3] Clinically this disease is easily confused with neck malignancy.Here, we would like to describe a rare case of type 3IgG4-SC that lacked pancreatic lesion and was accompanied by KT and lymphadenitis manifesting itself as a mass in the neck, which was originally suspected as CC and neck malignancy.
BACKGROUND: Pancreatic stellate cells(PSCs) play a critical role in the pathogenesis of pancreatic fibrosis and have emerging functions as progenitor cells,immune cells or intermediaries in pancreatic exocrine secretion. Increasing evidence has shown that desmin as an exclusive cytoskeleton marker of PSC is only expressed in part of these cells. This study was to establish a desmin-positive PSC cell line and evaluate its actions on pancreatic fibrosis,inflammation and immunity.METHODS: The presence of cytoskeletal proteins,integrin α5β1 or TLR4,was determined by immunocytochemistry while the production of desmin,collagen I,MMP-1,MMP-2,TIMP-2,or CD14 was evaluated by Western blotting. The levels of desmin,collagen I,IL-1 and IL-6 m RNA were determined by real-time quantitative PCR. The secretion of cytokines was detected by ELISA. Cell function was assessed using adhesion,migration,or proliferation assays. RESULTS: A stable activated rat PSC cell line(designated as RP-2) was established by RSV promoter/enhancer-driven SV40 large T antigen expression. RP-2 cells retained typical PSC properties,exhibited a myofibroblast-like phenotype and persistently produced desmin. The cells produced collagen I protein,matrix metalloproteinases and inhibitors thereof. RP-2 cells demonstrated typical PSC functions,including proliferation,adherence,and migration,the latter two of which occurred in response to fibronectin and were mediated byintegrin α5β1. TLR4 and its response genes including proinflammatory cytokines(IL-1,IL-6,TNF-α) and chemotactic cytokines(MCP-1,MIP-1α,Rantes) were produced by RP-2 cells and activated by LPS. LPS-induced IL-1 or IL-6 m RNA expression in this cell line was fully blocked with My D88 inhibitor.CONCLUSION: RP-2 cells provide a novel tool for analyzing the properties and functions of PSCs in the pathogenesis of fibrosis,inflammation and immunity in the pancreas.
