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-M6 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-organelle antibodies in a drug-induced hepatitis.
Pons
C
C
Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, URA 400 CNRS, Université René Descartes, Paris, France.
Dansette
P M
PM
Gregeois
J
J
Homberg
J C
JC
Billett
E E
EE
Mansuy
D
D
D000918:Antibody Specificity; D000937:Antigen-Antibody Reactions; D001323:Autoantibodies / Q000096:biosynthesis; D056486:Chemical and Drug Induced Liver Injury / Q000276:immunology*; D004342:Drug Hypersensitivity; D005260:Female; D006801:Humans; D007490:Iproniazid / Q000009:adverse effects / Q000276:immunology*; D007527:Isoenzymes / Q000276:immunology* / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D008928:Mitochondria / Q000201:enzymology*; D008930:Mitochondria, Liver / Q000201:enzymology* / Q000276:immunology*; D008995:Monoamine Oxidase / Q000276:immunology* / Q000378:metabolism; D010293:Pargyline / Q000378:metabolism; D010920:Placenta / Q000201:enzymology; D011247:Pregnancy
D001323:Autoantibodies; D007527:Isoenzymes; D010293:Pargyline; D007490:Iproniazid; D008995:Monoamine Oxidase