Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04040 (Catalase)
 3,577 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown aetiology. Recent studies have shown that genetic factors and both cellular and humoral immunological abnormalities are important in the pathogenesis of PSC. The most prominent autoantibodies in PSC are anti-neutrophil cytoplasmic antibodies (ANCA). The autoepitopes of ANCA in PSC are not well defined. The aim of this study was to identify corresponding ANCA autoantigens in patients with PSC. A biochemical approach with enrichment and partial purification of soluble neutrophil proteins, detection of autoantibodies by Western blot and partial amino acid sequencing were used. Two new autoantigen/autoantibody systems in patients with PSC were detected: catalase and alpha-enolase. The presence of catalase autoantibodies in 9/15 (60%) and alpha-enolase autoantibodies in 4/15 (27%) was confirmed by ELISA and Western blot. Furthermore, we showed immunoreactions of PSC sera with human biliary epithelial cells, showed the reduction of fluorescence in anti-catalase absorption experiments and observed partial co-localization of anti-catalase antibodies and PSC sera in double-staining experiments on biliary epithelial cells. The anti-catalase antibody-positive PSC patients had a more severe course of disease with a significantly higher alkaline phosphatase compared with the anti-catalase-negative PSC patients (P < 0.06). All ulcerative colitis control sera were anti-catalase antibody-negative. The identified antigens catalase and alpha-enolase can partly explain the ANCA fluorescence on ethanol-fixed and formaldehyde-fixed granulocytes in patients with PSC. Catalase is an important anti-oxidant enzyme and prevents cell damage from highly reactive oxygen-derived free radicals. Catalase autoantibodies might play a pathogenic role in patients with PSC. Our findings support the hypothesis that oxidative stress is one of the pathogenic mechanisms in patients with PSC.
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PMID:Identification and characterization of autoantibodies against catalase and alpha-enolase in patients with primary sclerosing cholangitis. 964 23

To discuss exhaustively: clinical, serological and pathologic aspects of primary sclerosing cholangitis (PSC); recent advantages in the knowledge of the disease's pathogenesis, therapeutic approaches that still appear today less preferable than liver transplantation. We have reviewed the most important researches on PSC of recent years. PSC is characterized by chronic inflammation of the main bile ducts, except for the gallbladder. HLA-B8 and HLA-DR3 haplotypes have been associated with PSC. It is probable that PSC is an organ-specific disease. Some studies have shown the presence of antibodies against the cytoplasm of neutrophils (ANCA) in the serum of more than 50% of patients, and the presence of anticatalase antibodies in 60% of patients. ANCAs induce leukocyte metabolic activation, that forms H2O2 and the anion superoxide O-2, which in turn impair components of both cell and cellular matrix. Catalase is mainly found in the liver; it is active in the "antioxidative defense system" against toxic O2 metabolites. Anticatalase antibodies are directed against an essential region of catalases, by inhibiting their enzymatic functions. In these conditions, a state of oxidative stress is determined by imbalanced ratio of oxidative to antioxidative factors, due to effective production of radical species as well as to simultaneous failure of antiradical defenses. Radical stress results in irreversible impairment of tissues. In PSC, primary lesions seem to be secondary to the production of radicals by ANCAs, deposited immunocomplex, complementary proteins and bacterial toxins. The subsequent lysis of bile epithelial cells seems to release catalases, that are thought to act as "nonself" once recognized by the immunocompetent system. Since the neoantigen catalase seems to be highly expressed in PSC patients, it may easily associate itself with MHC molecules for presentation to the immune system. Thus, in turn, B lymphocytes would be forced to produce anticatalase antibodies. Since anticatalase antibodies inhibit catalases, it can be hypothesized that they play a role in the pathogenesis of PSC. From a therapeutic viewpoint, the only effective cure is transplantation.
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PMID:Primary sclerosing cholangitis. 1243 13