{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,5,18]],"date-time":"2024-05-18T02:48:33Z","timestamp":1716000513966},"reference-count":44,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2006,6,30]],"date-time":"2006-06-30T00:00:00Z","timestamp":1151625600000},"content-version":"vor","delay-in-days":29,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of the New York Academy of Sciences"],"published-print":{"date-parts":[[2006,6]]},"abstract":"<jats:p><jats:bold><jats:sc>Abstract:\u2002<\/jats:sc><\/jats:bold>  <jats:bold>As azathioprine is one of the standard immunosuppressive drugs used for treatment of patients with different chronic inflammatory diseases, the effect of the azathioprine metabolizing enzyme thiopurine methyltransferase (TPMT) activity on incidence of adverse events (AE) was examined. In addition, potential correlations between the concentration of the azathioprine metabolite 6\u2010thioguanine nucleotide (6\u2010TGN) in erythrocytes (RBC) and inflammatory disease activity as well as hematological AE were investigated. TPMT activities were investigated prospectively in 139 patients (35 male, 104 female) with chronic inflammatory diseases [systemic lupus erythematosus (SLE, 38), progressive systemic sclerosis (PSS, 13), Wegener's granulomatosis (4), rheumatoid arthritis (RA, 5), and other chronic inflammatory diseases (79)]. In addition, 6\u2010TGN concentrations were investigated in a second cohort of 58 patients (17 patients with SLE, 5 with PSS, 5 with vasculitides, 4 with undifferentiated connective tissue diseases, 1 with dermatomyositis, 1 with Sj\u00f6gren's syndrome, 1 with RA, 20 with Crohn's disease, and 4 with ulcerative colitis) prior to and during therapy with azathioprine. The distribution of activities of TPMT in 139 patients showed a normal Gaussian distribution in the Caucasian population. Within the group of 96 patients taking azathioprine, known azathioprine\u2010related AE could be observed: minor AE (sickness, rash, and increase in cholestasis parameters) in 11 patients (11.4%), and severe AE (bone marrow toxicity) in 7 patients (7.3%). Below a \u201ccutoff\u201d value of 11.9 nmol\/mL RBC \u00d7 h of TPMT activity, AE were significantly more frequent. In the second cohort of patients, no significant correlations could be observed between 6\u2010TGN concentrations and parameters of disease activity. Reduced activity of TPMT in patients with chronic inflammatory diseases requiring immunosuppressive therapy with azathioprine, especially below a distinct cutoff, appears to inherit a substantial risk for development of AE.<\/jats:bold> <\/jats:p>","DOI":"10.1196\/annals.1351.048","type":"journal-article","created":{"date-parts":[[2006,7,19]],"date-time":"2006-07-19T19:35:49Z","timestamp":1153337749000},"page":"477-491","source":"Crossref","is-referenced-by-count":18,"title":["Impact of Thiopurine Methyltransferase Activity and 6\u2010Thioguanine Nucleotide Concentrations in Patients with Chronic Inflammatory Diseases"],"prefix":"10.1111","volume":"1069","author":[{"given":"J\u00d6RG","family":"SCHEDEL","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"ANDREA","family":"G\u00d6DDE","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"EKKEHARD","family":"SCH\u00dcTZ","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"TIM A.","family":"BONGARTZ","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"BERNHARD","family":"LANG","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00dcRGEN","family":"SCH\u00d6LMERICH","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"ULF","family":"M\u00dcLLER\u2010LADNER","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,6,30]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780170107"},{"key":"e_1_2_5_3_2","first-page":"89","article-title":"Activities of immunosuppressive agents vitro. 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