Analysis of the clinical relevance of antimitochondrial antibodies to the β- and γ-subunits of the F1F0-ATPase in patients with primary biliary cirrhosisReportar como inadecuado




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BMC Gastroenterology

, 12:152

Hepatobiliary and pancreatic disorders

Abstract

BackgroundIn a recent study we showed that in patients with primary biliary cirrhosis PBC being positive or negative for anti-M2 antibodies reacting with the 2-oxoacid-dehydrogenase complex ODC also antibodies to the beta- and gamma-subunits of F1F0-ATPase anti-β, anti-γ occur. This is a mitochondrial enzyme but parts are also expressed on plasma membranes of endothelial cells. Here we wanted to analyse in more detail their clinical relevance.

MethodsFifty-nine untreated and histologically defined PBC patients who had been followed for at least five years were included into the study 51 anti-M2 positive, 8 anti-M2 negative. Twenty-three of them were treated in the follow up with ursodeoxycholic acid UDCA, eight received during a trial methotrexate MTX. In 13 patients orthotopic liver transplantation OLT had to be performed. Serum samples before and during therapy were available. Patients were analysed with respect to laboratory parameters, disease activity and histological stages.

Patients’ sera were tested by ELISA for IgG- and IgM-antibodies against the beta- and gamma-subunits which had been recombinant expressed in E.coli and highly purified by electro-elution from SDS-gels after electrophoresis.

ResultsFifty-nine percent of the anti-M2 positive and 50% of the anti-M2 negative PBC patients had anti-β- and-or anti-γ-antibodies. There were no differences between anti-β- and-or anti-γ-antibody positive or negative patients with respect to biochemical parameters, immunoglobulins, histological stages or disease activity. Antibody reactivity significantly decreased during UDCA and MTX-treatment and also after OLT.

ConclusionsAntibodies to the β- and γ-subunits of F1F0-ATPase occur in anti-M2 positive and –negative PBC but do not have any relevance with respect to clinical activity or prognosis. However, in contrast to the anti-M2 antibodies they decrease during UDCA and immunosuppressive therapy.

KeywordsPrimary biliary cirrhosis Antimitochondrial antibodies Anti-M2-ODC F1F0-ATPase β-subunit γ-subunit AbbreviationsAIHautoimmune hepatitis

AMAantimitochondrial antibodies

ANAantinuclear antibodies

ALATalanine aminotransferase

ASATaspartate aminotransferase

APalkaline phosphatase

ATPAdenosinetriphosphate

BCOADCbranched-chain 2-oxo-acid dehydrogenase complex

ELISAenzyme linked immunosorbent assay

γGTgamma-glutamyltransferase

IFTimmunofluorescence test

Igimmunoglobulin

MTXmethotrexate

ODC2-oxoacid-dehydrogenase complex

OGDC2-oxoglutarate dehydrogenase complex

OLTorthotopic liver transplantation

PBCprimary biliary cirrhosis

PSCprimary sclerosing cholangitis

PDCpyruvate dehydrogenase

SDSsodiumdodecylsulfate

UDCAursodeoxycholic acid.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-230X-12-152 contains supplementary material, which is available to authorized users.

Dominik Nann, Christoph P Berg contributed equally to this work.

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Autor: Dominik Nann - Christoph P Berg - Beate E Preuß - Reinhild Klein

Fuente: https://link.springer.com/



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