IgG3 Is the Dominant Subtype of Anti-isoniazid Antibodies in Patients with Isoniazid-Induced Liver Failure

Isoniazid (INH) therapy is associated with a significant incidence of idiosyncratic liver failure. We recently reported eight cases of INH-induced liver failure in which patients had antidrug and anticytochrome P450 antibodies. However, it was unclear what role these antibodies play in the mechanism...

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Bibliographic Details
Published in:Chemical research in toxicology 2014-05, Vol.27 (5), p.738-740
Main Authors: Metushi, Imir G, Lee, William M, Uetrecht, Jack
Format: Article
Language:English
Subjects:
Antitubercular Agents - adverse effects
Antitubercular Agents - immunology
Chemical and Drug Induced Liver Injury - blood
Chemical and Drug Induced Liver Injury - immunology
Chemical and Drug Induced Liver Injury - pathology
Humans
Immunoglobulin G - immunology
Isoniazid - adverse effects
Isoniazid - immunology
Liver - drug effects
Liver - immunology
Liver - pathology
Liver Failure - blood
Liver Failure - chemically induced
Liver Failure - immunology
Liver Failure - pathology
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Summary:Isoniazid (INH) therapy is associated with a significant incidence of idiosyncratic liver failure. We recently reported eight cases of INH-induced liver failure in which patients had antidrug and anticytochrome P450 antibodies. However, it was unclear what role these antibodies play in the mechanism of INH-induced liver injury. Here, we report that the dominant isotype of anti-INH antibodies was IgG, with IgG3 being the dominant subtype. IgG3 antibodies are associated with a Th1-type immune response and fix complement. IgG3 antibodies have been associated with other forms of liver injury and may play a pathogenic role in INH-induced liver injury.
ISSN:0893-228X
1520-5010
DOI:10.1021/tx500108u