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Background: In 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. Methods: Fifty-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. Results: Fifty-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. Conclusions: Antibodies 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. [ABSTRACT FROM AUTHOR]

Background: In 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.Methods: Fifty-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.Results: Fifty-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.Conclusions: Antibodies 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. [ABSTRACT FROM AUTHOR]

Mistletoe extracts exert immunomodulatory properties on immunocompetent cells of the innate as well as the specific immune system. These effects have been mainly ascribed to mistletoe lectin 1 (ML-1) present in most of the extracts. However, it became evident that also other components of these extracts may induce immunological reactions, and especially viscotoxins (VT) may be of relevance. Aim of the study was, therefore, to evaluate whether VT like ML-1 could activate B-cells and lead to the production of VT-specific antibodies. Sera from 26 patients with different tumours who were treated with the mistletoe extract ABNOBAviscum Mali (AM) 4 for at least 18 weeks were analysed before therapy and after 3, 6, 9, 12, and 18 weeks. Sera were tested by ELISA against the four viscotoxins A1, A2, A3, B, as well as against ML-1. Within the observation period twenty-four (92%) of the 26 patients developed antibodies to at least one of the four VT and 25 (96%) to ML-1. In most instances, anti-VT antibodies appeared after 6-9 weeks of treatment. The antibodies were predominantly of the IgG type belonging preferentially to the IgG1 and IgG3 subclass. IgE antibodies were found only to VT-B and to ML-1. There was no relation between the development of antibodies to VT and ML-1, and also cross-reactivity could be excluded with high probability. These data indicate that not only ML-1 but also VT induce immunological responses in patients treated with mistletoe extracts. Whether there is any relationship to the postulated anti-tumour effect of mistletoe extracts has, however, still to be evaluated.