TNFSF9 expression in primary biliary cirrhosis and its clinical significance

Primary biliary cirrhosis (PBC) is a TH1/Th17 biased autoimmune disease of the medium and small bile ducts. The role of the costimulatory TNFSF9 (4-1BBL) in PBC progress was investigated by comparing its cell surface expression in peripheral blood mononuclear cells (PBMC) by flow cytometry, its mRNA expression in PBMCs by QRT-PCR and its serum concentrations in PBC patients vs. healthy controls. The TNFSF9 expression levels were compared with Mayo risk scores, PBC stages, IL-18 serum levels, total bilirubin (TBIL), and gamma glutamyltransferase (gamma-GT). The PBC patients expressed significantly greater levels of membrane bound TNFSF9, mRNA on peripheral blood mononuclear cells (PBMC), and soluble TNFSF9 (P<0.05) than healthy controls. Stage III and IV PBC subjects showed significantly reduced TNFSF9 mRNA than stage I and II. The TBIL, gamma-GT, and IL-18 were greatly increased in PBC patients compared with healthy controls. Stage II, III, and IV patients exhibited significantly higher IL-18 levels than stage I subjects. TNFSF9 mRNA significantly correlated with serum TBIL, gamma-GT, and IL-18 (P<0.05, P<0.01, P<0.01). Thus, TNFSF9 mRNA levels in PBMC may be associated with PBC progression, provide new clues for monitoring its condition and pathogenesis.