{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T06:10:48Z","timestamp":1792131048073,"version":"4.4.0"},"reference-count":33,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2013,8,20]],"date-time":"2013-08-20T00:00:00Z","timestamp":1376956800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Experimental Allergy"],"published-print":{"date-parts":[[2013,9]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Patients with Stevens\u2013Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) are often exposed simultaneously to a few potentially culprit drugs. However, both the standard lymphocyte transformation tests (LTT) with proliferation as the assay end\u2010point as well as skin tests, if done, are often negative.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>As provocation tests are considered too dangerous, there is an urgent need to identify the relevant drug in SJS\/TEN and to improve sensitivity of tests able to identify the causative drug.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Fifteen patients with SJS\/TEN with the ALDEN score \u2265\u00a06 and 18 drug\u2010exposed controls were included. Peripheral blood mononuclear cells (PBMC) were isolated and cultured under defined conditions with drugs. LTT was compared to the following end\u2010points: cytokine levels in cell culture supernatant, number of granzyme B secreting cells by ELISpot and intracellular staining for granulysin and IFN\u03b3 in CD3<jats:sup>+<\/jats:sup>\u00a0CD4<jats:sup>+<\/jats:sup>, CD3<jats:sup>+<\/jats:sup>\u00a0CD8<jats:sup>+<\/jats:sup> and NKp46<jats:sup>+<\/jats:sup> cells. To further enhance sensitivity, the effect of IL\u20107\/IL\u201015 pre\u2010incubation of PBMC was evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Lymphocyte transformation tests was positive in only 4\/15 patients (sensitivity 27%, CI: 8\u201355%). Similarly, with granzyme B\u2010ELISpot culprit drugs were positive in 5\/15 patients (sensitivity 33%, CI: 12\u201362%). The expression of granulysin was significantly induced in NKp46<jats:sup>+<\/jats:sup> and CD3<jats:sup>+<\/jats:sup>\u00a0CD4<jats:sup>+<\/jats:sup> cells (sensitivity 40%, CI: 16\u201368% and 53%, CI: 27\u201379% respectively). Cytokine production could be demonstrated in 38%, CI: 14\u201368% and 43%, CI: 18\u201371% of patients for IL\u20102 and IL\u20105, respectively, and in 55%, CI: 23\u201383% for IFN\u03b3. Pre\u2010incubation with IL\u20107\/IL\u201015 enhanced drug\u2010specific response only in a few patients. Specificities of tested assays were in the range of 95 (CI: 80\u201399%)\u2013100% (CI: 90\u2013100%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Clinical Relevance<\/jats:title><jats:p>Granulysin expression in CD3<jats:sup>+<\/jats:sup>\u00a0CD4<jats:sup>+<\/jats:sup>, Granzyme B\u2010ELISpot and IFN\u03b3 production considered together provided a sensitivity of 80% (CI: 52\u201396%) and specificity of 95% (80\u201399%). Thus, this study demonstrated that combining different assays may be a feasible approach to identify the causative drug of SJS\/TEN reactions; however, confirmation on another group of patients is necessary.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cea.12145","type":"journal-article","created":{"date-parts":[[2013,5,14]],"date-time":"2013-05-14T03:27:41Z","timestamp":1368502061000},"page":"1027-1037","source":"Crossref","is-referenced-by-count":123,"title":["<i>In vitro<\/i> drug causality assessment in Stevens\u2013Johnson syndrome \u2013 alternatives for lymphocyte transformation test"],"prefix":"10.1111","volume":"43","author":[{"given":"G.","family":"Porebski","sequence":"first","affiliation":[{"name":"ADR\u2010AC GmbH Bern Switzerland"},{"name":"Division of Allergology Department of Rheumatology, Clinical Immunology and Allergology, Inselspital University of Bern Bern Switzerland"},{"name":"Department of Clinical and Environmental Allergology Jagiellonian University Medical College Krakow Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Pecaric\u2010Petkovic","sequence":"additional","affiliation":[{"name":"ADR\u2010AC GmbH Bern Switzerland"},{"name":"Division of Allergology Department of Rheumatology, Clinical Immunology and Allergology, Inselspital University of Bern Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Groux\u2010Keller","sequence":"additional","affiliation":[{"name":"ADR\u2010AC GmbH Bern Switzerland"},{"name":"Division of Allergology Department of Rheumatology, Clinical Immunology and Allergology, Inselspital University of Bern Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Bosak","sequence":"additional","affiliation":[{"name":"Department of Neurology Jagiellonian University Medical College Krakow  Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. T.","family":"Kawabata","sequence":"additional","affiliation":[{"name":"Drug Safety Research and Development Pfizer Groton CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. 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