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Research Article Free access | 10.1172/JCI114660

Anti-liver endoplasmic reticulum autoantibodies are directed against human cytochrome P-450IA2. A specific marker of dihydralazine-induced hepatitis.

M Bourdi, D Larrey, J Nataf, J Bernuau, D Pessayre, M Iwasaki, F P Guengerich, and P H Beaune

Institut National de la Santé et de la Recherche Médicale U 75, CHU Necker-Enfants-Malades, Paris, France.

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Institut National de la Santé et de la Recherche Médicale U 75, CHU Necker-Enfants-Malades, Paris, France.

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Institut National de la Santé et de la Recherche Médicale U 75, CHU Necker-Enfants-Malades, Paris, France.

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Institut National de la Santé et de la Recherche Médicale U 75, CHU Necker-Enfants-Malades, Paris, France.

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Institut National de la Santé et de la Recherche Médicale U 75, CHU Necker-Enfants-Malades, Paris, France.

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Institut National de la Santé et de la Recherche Médicale U 75, CHU Necker-Enfants-Malades, Paris, France.

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Institut National de la Santé et de la Recherche Médicale U 75, CHU Necker-Enfants-Malades, Paris, France.

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Institut National de la Santé et de la Recherche Médicale U 75, CHU Necker-Enfants-Malades, Paris, France.

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Published June 1, 1990 - More info

Published in Volume 85, Issue 6 on June 1, 1990
J Clin Invest. 1990;85(6):1967–1973. https://doi.org/10.1172/JCI114660.
© 1990 The American Society for Clinical Investigation
Published June 1, 1990 - Version history
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Abstract

Sera from patients with dihydralazine-induced hepatitis were shown to contain anti-liver microsomal autoantibodies (anti-LM) by indirect immunofluorescence. These anti-LM antibodies were different from anti-liver/kidney microsomes (anti-LKM) 1 or 2 autoantibodies which have been previously described. Sera recognized a single 53,000 = Mr polypeptide in human liver microsomes as judged by immunoblotting, and the target antigen was identified as cytochrome P-450IA2 (P-450IA2) by (a) comparison of immunoblotting patterns with anti-human P-450IA2 and anti-rat P-450IA2 and with five anti-LM sera, and (b) specific immunoinhibition of microsomal ethoxyresorufin and phenacetin O-deethylation activities (both P-450IA2 supported reactions) by anti-LM antibodies. Finally, purified human P-450IA2 was recognized by these anti-LM sera. The anti-LM antibodies are specific for the disease because none of the other antisera tested behaved in the same manner as anti-LM, even those from patients treated with dihydralazine and without hepatic disease. A possible role of P-450IA2 in the metabolism of dihydralazine was suggested by competitive inhibition of ethoxyresorufin-O-deethylase observed in microsomal incubations. Thus, a new example is presented in which a cytochrome P-450 may be a target for autoantibodies in drug-induced hepatitis.

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