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Relevance of the inner mitochondrial membrane enzyme F 1 F 0 ‐ ATP ase as an autoantigen in autoimmune liver disorders
Author(s) -
Preuß Beate,
Berg Christoph,
Dengjel Jörn,
Stevanovic Stefan,
Klein Reinhild
Publication year - 2012
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/j.1478-3231.2011.02630.x
Subject(s) - primary biliary cirrhosis , antibody , medicine , autoimmune hepatitis , connective tissue , connective tissue disease , immunology , cirrhosis , hepatitis , autoimmune disease , autoantibody , pathology
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 ‐ ATP ase subunits α, β, γ, δ and ε. In this study, we examined whether this enzyme is, indeed, a target antigen in PBC . 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, S jögren disease, systemic sclerosis) and 25 blood donors. The F 1 ‐ ATP ase‐subunits α‐δ were recombinantly expressed in E scherichia coli , purified and applied to ELISA and W estern blotting. 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. Conclusions Antibodies to the β‐ and γ‐subunits of F 1 ‐ ATP ase are further AMA s in PBC but occur also in other autoimmune liver disorders; they may be, therefore, indicators for a general autoimmune process of the liver.