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Relevance of the inner mitochondrial membrane enzyme F1F0-ATPase as an autoantigen in autoimmune liver disorders.
- Source :
-
Liver international : official journal of the International Association for the Study of the Liver [Liver Int] 2012 Feb; Vol. 32 (2), pp. 249-57. Date of Electronic Publication: 2011 Sep 08. - Publication Year :
- 2012
-
Abstract
- Background and Aims: Recently, a non-M2-related mitochondrial 60 kDa protein found to be recognized by antimitochondrial antibody (AMA) negative sera from patients with primary biliary cirrhosis (PBC) has been shown to contain parts of the five F(1)-ATPase subunits α, β, γ, δ and ε. In this study, we examined whether this enzyme is, indeed, a target antigen in PBC.<br />Methods: Analysed were 60 AMA-positive/anti-M2-negative and 103 anti-M2-positive PBC patients, 46 patients with autoimmune hepatitis (AIH), 35 patients with primary sclerosing cholangitis (PSC), 110 patients with viral hepatitis, 40 patients with inflammatory bowel diseases (IBD), 33 patients with connective tissue diseases (systemic lupus erythematosus, mixed connective tissue disease, Sjögren disease, systemic sclerosis) and 25 blood donors. The F(1)-ATPase-subunits α-δ were recombinantly expressed in Escherichia coli, purified and applied to ELISA and Western blotting.<br />Results: In all, 40 of the 60 AMA-positive/anti-M2-negative (67%) and 44 (43%) of the 103 anti-M2-positive PBC-sera reacted with at least one of the F(1)-subunits α-δ. The β- and γ-subunits were preferentially recognized. However, also up to 57% of patients with AIH and 34% of patients with PSC had anti-β- or γ-antibodies, while patients with viral hepatitis had these antibodies in up to 13%. Patients with IBD had anti-β and anti-γ-antibodies in up to 20 and 5% respectively. None of the patients with connective tissue diseases had antibodies to the β- and only 6% to the γ-subunit. Sera from healthy blood donors were negative.<br />Conclusions: Antibodies to the β- and γ-subunits of F(1)-ATPase are further AMAs in PBC but occur also in other autoimmune liver disorders; they may be, therefore, indicators for a general autoimmune process of the liver.<br /> (© 2011 John Wiley & Sons A/S.)
- Subjects :
- Adolescent
Adult
Aged
Child
Cholangitis, Sclerosing blood
Cholangitis, Sclerosing enzymology
Cholangitis, Sclerosing immunology
Connective Tissue Diseases blood
Connective Tissue Diseases enzymology
Connective Tissue Diseases immunology
Female
Hepatitis, Autoimmune blood
Hepatitis, Autoimmune enzymology
Hepatitis, Viral, Human blood
Hepatitis, Viral, Human enzymology
Hepatitis, Viral, Human immunology
Humans
Inflammatory Bowel Diseases blood
Inflammatory Bowel Diseases enzymology
Inflammatory Bowel Diseases immunology
Liver pathology
Male
Middle Aged
Protein Subunits genetics
Protein Subunits immunology
Proton-Translocating ATPases classification
Proton-Translocating ATPases genetics
Young Adult
Autoantibodies blood
Autoantigens immunology
Hepatitis, Autoimmune immunology
Mitochondrial Membranes enzymology
Proton-Translocating ATPases immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1478-3231
- Volume :
- 32
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Liver international : official journal of the International Association for the Study of the Liver
- Publication Type :
- Academic Journal
- Accession number :
- 22098431
- Full Text :
- https://doi.org/10.1111/j.1478-3231.2011.02630.x