AbstractBackground and AimsRecently, 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.MethodsAnalysed 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 Escherichia coli, purified and applied to ELISA and Western blotting.ResultsIn 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.ConclusionsAntibodies 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.