Relevance of the inner mitochondrial membrane enzyme F1F0- ATPase as an autoantigen in autoimmune liver disorders.

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 F₁- ATPase 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, Sjögren disease, systemic sclerosis) and 25 blood donors. The F₁- ATPase-subunits α-δ were recombinantly expressed in E scherichia coli, purified and applied to ELISA and Western 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 F₁-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 F₁- 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. [ABSTRACT FROM AUTHOR]