1. Sulphite oxidase (SO) - a mitochondrial autoantigen as target for humoral and cellular immune reactions in primary sclerosing cholangitis.
- Author
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Preuß BE, Berg CP, Werner C, Plankenhorn S, Malek NP, and Klein R
- Subjects
- Adolescent, Adult, Aged, B-Lymphocytes physiology, Cholagogues and Choleretics therapeutic use, Cholangitis, Sclerosing drug therapy, Epitope Mapping, Female, Gene Expression, Humans, Immunoglobulin G blood, Immunoglobulin M blood, Lymphocyte Activation, Male, Middle Aged, Sulfite Oxidase genetics, Th2 Cells physiology, Ursodeoxycholic Acid therapeutic use, Young Adult, Autoantibodies blood, Autoantigens immunology, Cholangitis, Sclerosing immunology, Immunity, Cellular, Immunity, Humoral, Mitochondria enzymology, Sulfite Oxidase immunology
- 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.
- Published
- 2018
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