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Sulphite oxidase (SO) - a mitochondrial autoantigen as target for humoral and cellular immune reactions in primary sclerosing cholangitis.
- Source :
-
BMC gastroenterology [BMC Gastroenterol] 2018 May 02; Vol. 18 (1), pp. 58. Date of Electronic Publication: 2018 May 02. - Publication Year :
- 2018
-
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.<br />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.<br />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).<br />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.
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 1471-230X
- Volume :
- 18
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- BMC gastroenterology
- Publication Type :
- Academic Journal
- Accession number :
- 29720090
- Full Text :
- https://doi.org/10.1186/s12876-018-0787-x