Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The tuberculostatic agent isoniazid has been implicated in inducing various idiosyncratic reactions including drug-induced lupus. The mechanism is unknown but may involve a reactive metabolite of the drug. Isoniazid was oxidized by activated leukocytes to isonicotinic acid. Myeloperoxidase is likely the enzyme in the leukocyte involved, since the oxidation was inhibited by azide, which inhibits myeloperoxidase, and by catalase, which catalyzes the breakdown of hydrogen peroxide. The same metabolic profile was observed when isoniazid was incubated with purified myeloperoxidase and hydrogen peroxide. The rate of the reaction was increased in the presence of chloride. Hypochlorous acid was also able to oxidize isoniazid to isonicotinic acid. Isoniazid, or an oxidative product, inhibited the reaction when high initial substrate concentrations were used. Isoniazid is oxidized by activated leukocytes, possibly to a reactive intermediate, which may have implications for isoniazid-induced lupus.
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PMID:Metabolism of isoniazid by activated leukocytes. Possible role in drug-induced lupus. 135 11

The haemolytic activities of the complement alternative pathway and factor B were studied using a 51Cr-release assay in 77 sera from patients with systemic lupus erythematosus (SLE). These values were compared to those of several complement components and of the regulatory proteins beta H and C3b INA. There was a significant decrease in the alternative pathway activity, which correlated with a decrease in the haemolytic activity of factor B and with the activity of the classical pathway. There was a significant decrease in the level of one regulatory protein beta 1H, while the level of the other regulatory protein, C3b INA, was increased; however, there was a positive correlation between these two parameters. The results obtained suggest that the decreased activity of the alternative pathway observed in SLE reflects a consumption due to a triggering of the C3b amplification loop through the activation of the classical pathway. In one patient, an acquired deficiency of the capacity to activate the alternative pathway in the presence of inulin was observed.
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PMID:Evaluation of alternative pathway and factor B haemolytic activities in patients with systemic lupus erythematosus: correlations with the alternative pathway regulatory proteins. 616 79

Isoniazid (INH) treatment can cause serious liver injury and autoimmunity. There are now several lines of evidence that INH-induced liver injury is immune mediated, but this type of liver injury has not been reproduced in animals, possibly because immune tolerance is the dominant response of the liver. In this study, we immunized mice with isonicotinic acid (INA)-modified proteins and Freund's adjuvant, which led to mild experimental autoimmune hepatitis (EAH) with an increase in cells staining positive for F4/80, CD11b, CD8, CD4, CD45R, and KI67. We expected that subsequent treatment of mice with oral INH would lead to more serious immune-mediated liver injury, but paradoxically it markedly attenuated the EAH caused by immunization with INA-modified hepatic proteins. In addition, patients of the slow acetylator phenotype are at increased risk of INH-induced liver injury. Treatment of arylamine N-acetyltransferase-deficient Nat1/2(-/-) mice with INH for up to 5 weeks produced mild increases in glutamate and sorbitol dehydrogenase activities, but not severe liver injury. Female Nat1/2(-/-) mice treated with INH for 1, 3, or 7 days developed steatosis, an increase in Oil Red O staining, and abnormal mitochondrial morphology in the liver. A decrease in M1 and an increase in M2a and M2b macrophages was observed in female Nat1/2(-/-) mice treated with INH for 1, 3, or 7 days; these changes returned to baseline levels by day 35. These data indicate that INH has immunosuppressive effects, even though it is also known to induce autoantibody production and a lupus-like autoimmune syndrome in humans.
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PMID:Paradoxical attenuation of autoimmune hepatitis by oral isoniazid in wild-type and N-acetyltransferase-deficient mice. 2462 63

Three cases of lupus vulgaris developing at the site of BCG vaccination are reported. All the patients had lesions starting before the age of 15 years. Clinically and histologically the lesions 'were indistinguishable from spontaneous lupus vulgarism Treatment with streptomycin and isonicotinic acid hydrazide for 1 year produced complete resolution of lesions.
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PMID:Lupus Vulgaris Following Bcg Vaccination. 2819 47