HUMAN ANTI-MITOCHONDRIA AUTOANTIBODIES APPEARING IN IPRONIAZID-INDUCED IMMUNOALLERGIC HEPATITIS RECOGNIZE HUMAN LIVER MONOAMINE-OXIDASE-B

Anti-mitochondria (anti-M6) autoantibodies have been found in the seru m of patients with immunoallergic iproniazid (Marsilid)-induced hepati tis, but to date the identity of the protein antigen has not been dete rmined. Here we show, using immunoprecipitation of pargyline-labelled proteins, that among the mitochondrial proteins, liver MAO-B is specif ically recognized by the sera containing anti-M6 antibodies. Moreover the enzymatic activity of MAO-B towards phenylethylamine and tyramine is also suppressed after this immunoprecipitation, contrary to the MAO -A activity towards 5-hydroxy-tryptamine. As MAO is irreversibly inhib ited by iproniazid, these results suggest that the mechanism of iproni azid-induced appearance of anti-hid antibodies could be another exampl e of the reactive metabolite/enzyme haptenization mechanism already pr oposed in the case of tienilic acid for the appearance of anti-oganell e antibodies in a drug-induced hepatitis. (C) 1996 Academic Press, Inc .