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 serum of patients with immunoallergic iproniazid (Marsilid)-induced hepatitis, but to date the identity of the protein antigen has not been determined. Here we show, using immunoprecipitation of pargyline-labelled proteins, that among the mitochondrial proteins, liver MAO-B is specifically 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 inhibited by iproniazid, these results suggest that the mechanism of iproniazid-induced appearance of anti-hid antibodies could be another example of the reactive metabolite/enzyme haptenization mechanism already proposed in the case of tienilic acid for the appearance of anti-oganelle antibodies in a drug-induced hepatitis. (C) 1996 Academic Press, Inc.