Abstract:
BACKGROUND:In a recent study we had evidence that sulphite oxidase (SO) may be a relevant autoantigen in primary sclerosing cholangitis (PSC). Aim of the present study was, therefore, to analyse humoral and cellular immune-reactivity towards SO in these patients in more detail. METHODS:Sera from 53 patients with PSC (30 untreated and 23 treated with ursodeoxycholic acid [UDCA] at time of analysis), from 422 patients with different hepatic and non-hepatic disorders, and from 50 healthy individuals were tested by ELISA for antibodies against full-length-SO (SO-fl) and its three major domains expressed in E.coli (SO-I, SO-II, SO-III). For epitope-mapping, 29 overlapping peptides were used. Peripheral blood mononuclear cells (PBMC) were obtained from 33 PSC-patients and analysed for SO-induced proliferation, production of cytokines, and expression of the activation marker cluster of differentiation (CD) 69. RESULTS:43% of the 30 untreated and 26% of the 23 treated PSC-patients had IgG anti-SO-antibodies predominantly reacting with SO-fl, SO-I and SO-II. Antibody-reactivity decreased after UDCA-treatment. Prevalence and reactivity of anti-SO-antibodies were significantly higher in PSC than in patients with other hepatic and non-hepatic disorders. Epitope mapping revealed no distinct immuno-dominant regions within SO. Incubation of PBMC from PSC-patients (but not from controls) with SO-antigens revealed an activation of B-cells and a T-helper cell type-2 reaction pattern (production of interleukin [IL]-13, IL-10). CONCLUSIONS:PSC-patients show humoral and cellular immune response towards SO. Antibodies may be predominantly directed against conformational epitopes. SO enhances in vitro especially T-helper cell type-2 immune-reactions, which may be pro-fibrotic. SO is a detoxifying enzyme present also in bacteria; further studies analysing its role in the aetiology and pathogenesis in PSC may, therefore, be important.
journal_name
BMC Gastroenteroljournal_title
BMC gastroenterologyauthors
Preuß BE,Berg CP,Werner C,Plankenhorn S,Malek NP,Klein Rdoi
10.1186/s12876-018-0787-xsubject
Has Abstractpub_date
2018-05-02 00:00:00pages
58issue
1issn
1471-230Xpii
10.1186/s12876-018-0787-xjournal_volume
18pub_type
杂志文章abstract:BACKGROUND:Recent improvements in stone extraction implements and apparatus have lessened the complexity of the endoscopic bile duct stone treatment. However, despite confirmation of complete removal, cases of residual stones have been reported, which can result in recurrent biliary symptoms, cholangitis, and pancreati...
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pub_type: 杂志文章,多中心研究,随机对照试验
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pub_type: 杂志文章,多中心研究,随机对照试验
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