Hepatitis: Holdenrieder S

Kremer AE, Rust C, Eichhorn P, Beuers U, Holdenrieder S. · AMC Liver Center, S1-164, University of Amsterdam, Academic Medical Center, Amsterdam, The Netherlands. · Expert Rev Mol Diagn. · Pubmed #19298138 No free full text.

Abstract: Primary biliary cirrhosis, primary sclerosing cholangitis and autoimmune hepatitis are the three major immune-mediated liver diseases. The etiologies of primary biliary cirrhosis, primary sclerosing cholangitis and autoimmune hepatitis are largely unknown, but seem to be influenced by genetic and environmental factors. Autoantibodies can be found in nearly all patients with primary sclerosing cholangitis and autoimmune hepatitis, and in the vast majority of patients with primary sclerosing cholangitis. In addition, autoimmune hepatitis is associated with high concentrations of serum globulins. Enhanced liver cell death by apoptosis has been described in all of these liver diseases, although the precise mechanisms remain unclear. In general, apoptosis can be initiated via an extrinsic pathway that is triggered by engagement of death receptors on the cell surface, or via an intrinsic pathway that is induced by mitochondrial injury and is influenced by members of the Bcl-2 family. In both pathways, effector caspases are finally activated that cleave and degrade cell structures, resulting in the release of apoptotic products into the circulation. New diagnostic tests can detect these apoptotic markers and programmed cell death ligands such as Fas and Fas-ligands, nucleosomes, caspases, cytokeratin fragments, macrophage migration inhibitory factor, soluble intracellular adhesion molecule, natural killer cells group 2D and programmed death ligands. Several of these markers have been found to be altered in tissue and/or blood of immune-mediated liver diseases, some also in nonimmune-mediated liver diseases. Beyond their potential usefulness as additional diagnostic markers, they may be valuable for the estimation of disease severity and therapy monitoring. This review summarizes current knowledge on apoptotic mechanisms, death receptor ligands and circulating apoptotic markers in immune-mediated liver diseases.

Holdenrieder S, Eichhorn P, Beuers U, Samtleben W, Stieber P, Nagel D, Peterfi A, Steinle A, Salih HR. · Institute of Clinical Chemistry, University Hospital of Munich, 81377 Munich, Germany. · Anticancer Res. · Pubmed #17649819 No free full text.

Abstract: BACKGROUND: Proteolytic shedding of the immunostimulatory NKG2D ligands MICA and MICB from cancer cells constitutes a novel immune escape strategy that diminishes antitumor reactivity by NKG2D-bearing cytotoxic lymphocytes. In consequence, serum levels of soluble MICA and MICB are frequently found to be elevated in cancer disease. PATIENTS AND METHODS: As the diagnostic potential depends strongly on the organ-specific benign diseases and is affected by diseases involved in marker metabolism, both markers were analyzed by ELISA in sera of 141 patients with hepatic autoimmune diseases (34 autoimmune hepatitis, 35 primary sclerosing cholangitis, 72 primary biliary cirrhosis), 18 patients with acute bacterial infections, 21 patients with renal insufficiency, 13 patients with cholestasis and 62 healthy individuals. RESULTS: Similarly to healthy controls (median sMICA < 30 pg/mL; sMICB < 30 pg/mL), low levels of both markers were generally found in sera of patients with hepatic autoimmune diseases. In contrast, significantly elevated concentrations of sMICA and sMICB were observed in sera of patients with acute infections (median sMICA 890 pg/mL; sMICB 111 pg/mL), in those with renal insufficiency (sMICA 195 pg/mL; sMICB 50 pg/mL), and in those with cholestasis (sMICA 1058 pg/mL; sMICB 146 pg/mL). CONCLUSION: While hepatic autoimmune diseases have no general impact on the amount of circulating sMICA and sMICB, acute bacterial infections, renal insufficiency and cholestasis can lead to notably elevated serum levels of the NKG2D ligands.