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Origine des anticorps anti-tissus apparaissant dans les hépatites médicamenteuses de type immuno allergiques

Abstract : Auto-antibodies anti-LKM2 (anti-Liver Kidney Microsomes 2) had been detected in sera of hepatitis patients after tienilic acid (Diflurex, Selacryn) treatment by indirect immunofluorescence on rat liver slices. We had shown that these autoantibodies recognisze a human cytochrome P450 responsible also for the metabolisation of the drug, cytochrome P450 IIC9. We have proposed a mechanism for the appearance of the auto-antibodies and designed a study model to test it in animals. Using biochemical techniques we have shown that the antibodies react also to a homologous protein in liver of untreated rats, cytochrome P450-UTA (IIC11). This cross-reaction was used to understand the clinical test which use immunofluorescence on rat liver slices. Then we found that tienilic acid treatment of rats cause the appearance of the hepatocyte surface of a neoantigen which is recognized by anti-LKM2. In order to generalize this concept of apperance of anti-tissues, we have studied the anti-mitochondrial auto-antibodies anti-M6 found in the serum of patients having hepatitis after treatment with the MonoAmine oxidase inhibiting drug iproniazide (Marsilid). We have shown that anti-M6 recognize the monoamine oxidase B, which is also irreversibly inhibited by iproniazid. This is the third example of drug induced autoimmune hepatitis with apperance of anti-tissues antibodies directed against a protein which activates the drug metabolically.
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Submitted on : Saturday, June 20, 2020 - 2:32:27 PM
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Catherine Pons. Origine des anticorps anti-tissus apparaissant dans les hépatites médicamenteuses de type immuno allergiques. Biologie animale. Université Paris-Diderot - Paris VII, 1989. Français. ⟨tel-00653612v2⟩



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