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)

Fifteen patients with spontaneous systemic lupus erythematosus (SLE) have been phenotyped by determination of plasma isoniazid (INH) half-life. Seven patients had signs of renal insufficiency. Of the 15 patients, 13 were slow and only 2 rapid acetylators. No correlation was found between the plasma INH half-lives and the renal function. Thus, there is the same marked predominance of slow acetylators in patients with spontaneous SLE as in patients with the drug-induced SLE-like syndrome.
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PMID:Spontaneous systemic lupus erythematosus and acelylator phenotype. 84 61

Seventeen Indian and 13 Black patients were studied. From hospital admission data, systemic lupus erythematosus (SLE) appeared to be more common in Indians than in Blacks in Natal. Renal biopsy specimens were taken from 27 patients and histological examination showed renal changes to be present in 26 patients. The high incidence of renal involvement may be due to the patients presenting at a late stage. Histological examination revealed severe renal changes which correlated with albuminuria, low serum complement and raised blood urea values. Tuberculosis is still a very common disease in Blacks and various matters arose in this connection: (a) the development of tuberculosis as a complication of corticosteroid therapy in an unduly high number (3/30) of our patients suggests that routine isoniazid (INH) prophylaxis is warranted, particularly if the tuberculin skin test is positive, (b) patients presenting with serositis are usually considered to have tuberculosis; the diagnosis of SLE is therefore sometimes initially overlooked, and (c) despite the very widespread use of INH in Blacks, we encountered no case of drug-induced lupus erythematosus.
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PMID:Systemic lupus erythematosus in Black and Indian patients in Natal. 87 Sep 88

Patterns of antinuclear antibodies (ANA) occurring in individuals consuming lupus-activating drugs who have not developed systemic lupus erythematosus (SLE), may give insight into their mode of action as SLE triggering agents. We have studied the antigenic specificity of ANA induced by isoniazid (INH), anticonvulsants and chlorpromazine. ANA found in INH treated subjects are primarily directed at soluble nucleoprotein (sNP), an antigen which is physicochemically altered in vivo by INH. Antibodies to INH altered sNP were found in 78 per cent of 214 subjects receiving INH, while none had anti-DNA antibodies. Different anticonvulsants give rise to different patterns of ANA. Antibodies to Sm antigen were found only in patients receiving hydantoins. Antibodies to native and denatured DNA were found in 14 per cent and 22 per cent respectively, of 170 patients receiving anticonvulsants. Antibodies to denatured DNA were most frequently found in patients receiving chlorpromazine, which correlated with the known reactivity of this drug to denatured DNA.
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PMID:Patterns of antinuclear antibodies and lupus-activating drugs. 108 Feb

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

A case of lupus-vulgaris-like infection caused by Mycobacterium xenopi in a 62-year-old immunocompetent female patient is presented. A large cutaneous infiltration was seen in the right periorbital region. Histological examination revealed a granulomatous reaction of epithelioid cells and giant cells. M. xenopi was isolated from biopsy material and tuberculosis could be excluded. Isoniazid was effective in healing the lesion within a year. Such infections are well known for other mycobacteria but to our knowledge had not yet been described for M. xenopi. The characteristics of human infections with M. xenopi are summarized in a review of the literature and criteria for the diagnosis of atypical cutaneous mycobacterioses are proposed.
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PMID:[A lupus-vulgaris like atypical mycobacteriosis caused by Mycobacterium xenopi (lupus xenopi)]. 139 3

Isoniazid, a tuberculostatic agent, induced in some patients lupus-like syndrome. Pathomechanism of this autoimmune phenomenon is unknown, and it is suggested that is associated with disturbances in immunoregulatory processes. Human peripheral blood mononuclear cells or T cells were isolated from healthy donors and were stimulated with phytohemagglutinin or antibody against CD3 cell receptor antigen. Proliferation, measured as thymidine uptake, was determined in in vitro cultures of the cells. Isoniazid added to cell cultures decreased proliferation at higher doses, and produced a slight increase in proliferation in concentration 10(-5)-10(-6) M. Isoniazid alone has no mitogenic activity. The viability of the cells, determined as the Trypan blue exclusion test, was decreased only at the presence of the highest used dose of isoniazid (10(-2) M), thus the results were not influenced by the toxic effects of the drug.
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PMID:Studies on immunomodulatory properties of isoniazid. I. Effect of isoniazid on mitogen- and anti-CD3 antibody-induced proliferation of human peripheral blood mononuclear cells and T cells. 214 Oct 35

Isoniazid (INH) is one among many drugs capable of inducing autoantibodies and, in some cases, a lupus-like syndrome (LE). A longitudinal study was performed in 24 tuberculosis patients treated with INH to detect antibodies (A-AH) to total histones and fractions. Antinuclear antibodies were observed in two patients after treatment. Higher frequency of IgM-AH was also observed. IgM-AH binding to all fractions were observed in those serum samples exhibiting stronger ELISA reactivity. Conversely, binding to only H1 occurred when lower IgM-AH activity was tested. Correlations with clinical expressions of LE were not observed in the present study.
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PMID:[Clinical and biochemical characterization of isoniazid-induced auto-antibodies]. 225 21

A case of isoniazid (INH)-induced lupus occurring in a 62-year-old man is presented. He visited our hospital in May 1986 and a cavitary lesion was found in the right upper lobe on a chest roentgenogram. He had no previous history of treatment with antituberculotic agents. Though acid-fast bacilli were not found in his sputum, pulmonary tuberculosis was strongly suspected and INH, rifampicin and ethanbutol were administered. Four days after starting the treatment, minimal left pleural effusion was seen on chest X-ray film. Three months later he began to complain polyarthralgia in his digital joints. In a pleural effusion many lymphocytes were found; and the antinuclear antibody (ANA), the anti-extractable nuclear antigens (ENA) antibody, and the RNase resistant anti-ENA antibody were positive, and their titres were 20x, 1000x and 1000x, respectively, and the immune complex (IC) was 16.0 micrograms/ml (LT5). In blood serum, the ANA test the anti-ENA antibody and the RNase resistant anti-ENA antibody were positive with titres 40x, 640x and 640x respectively; and the IC was 14.0 micrograms/ml, and the RA test was positive. The improvement of clinical findings and disappearance of auto-antibodies seen after stopping INH confirmed the diagnosis as INH-induced lupus.
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PMID:[A cases of isoniazid-induced lupus]. 281 Sep 99

Isoniazid (INH) and hydralazine (HYD) are transglutaminase (TGase, E.C.2.3.2.13.) substrates containing catalytically recruitable hydrazyl groups. Since they can be expected to inhibit TGase-mediated cell functions by competing with physiological substrates, their effect upon allogeneically and lectin-induced proliferation of mononucleocytes and upon zymosan-induced chemiluminescence of phagocytes was studied. Both compounds inhibited chemiluminescence in a dose-dependent manner. ID50 of HYD was consistently below 20 microM, while that of INH was above 120 microM. Proliferation of immunocompetent cells was suppressed by HYD with an ID50 of 60 microM, INH was inhibitory only above 5000 microM. Analogs of both compounds not containing hydrazyl groups proved to be inactive. Control experiments indicated that inhibition is not due to toxicity or lipophilicity of the compounds, structural analogs lacking a hydrazyl moiety were inactive. It is suggested that, in vivo, HYD interferes with signal-induced TGase-dependent leucocyte functions essential for immunologic stability, and that the resultant dysregulation with disruption of self tolerance contributes to the HYD promoted lupus-like syndrome.
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PMID:Effects of hydrazyl group containing drugs on leucocyte functions: an immunoregulatory model for the hydralazine-induced lupus-like syndrome. 286 61

It has been suggested that kallikrein inhibition may predispose patients with the lupus inhibitor to thrombosis by interfering with the Factor XII-mediated activation of plasminogen. To further investigate this suggestion, the authors measured kallikrein inhibition in 19 patients with the lupus inhibitor. They found that kallikrein inhibition was greater than 100% of that of a normal plasma pool in all patients and greater than 125% in 11 of 19. Kallikrein inhibition was significantly correlated with C1-esterase inhibitor (C1S-INH) concentration, which they measured by rocket immunoelectrophoresis (r = +0.55, P less than 0.05). In three patients the C1S-INH was more than 30% greater than the kallikrein inhibition. Crossed immunoelectrophoresis for C1S-INH in these patients' plasma revealed an electrophoretic mobility identical with that of the normal plasma pool. The authors suggest that C1S-INH-mediated kallikrein inhibition, in conjunction with other coagulation abnormalities, predisposes patients with the lupus inhibitor to thrombosis.
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PMID:Kallikrein inhibition and C1-esterase inhibitor levels in patients with the lupus inhibitor. 311 30


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