{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T01:40:29Z","timestamp":1791855629344,"version":"4.3.4"},"reference-count":40,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5388","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[1998,10,16]]},"abstract":"<jats:p>Toxic epidermal necrolysis (TEN, Lyell's syndrome) is a severe adverse drug reaction in which keratinocytes die and large sections of epidermis separate from the dermis. Keratinocytes normally express the death receptor Fas (CD95); those from TEN patients were found to express lytically active Fas ligand (FasL). Antibodies present in pooled human intravenous immunoglobulins (IVIG) blocked Fas-mediated keratinocyte death in vitro. In a pilot study, 10 consecutive individuals with clinically and histologically confirmed TEN were treated with IVIG; disease progression was rapidly reversed and the outcome was favorable in all cases. Thus, Fas-FasL interactions are directly involved in the epidermal necrolysis of TEN, and IVIG may be an effective treatment.<\/jats:p>","DOI":"10.1126\/science.282.5388.490","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T05:43:20Z","timestamp":1027748600000},"page":"490-493","source":"Crossref","is-referenced-by-count":880,"title":["Inhibition of Toxic Epidermal Necrolysis by Blockade of CD95 with Human Intravenous Immunoglobulin"],"prefix":"10.1126","volume":"282","author":[{"given":"Isabelle","family":"Viard","sequence":"first","affiliation":[{"name":"I. Viard, P. Wehrli, R. Bullani, D. Salomon, J.-H. Saurat, L. E. French, Department of Dermatology, Geneva University Medical School, CH-1211 Geneva 4, Switzerland. P. Schneider, N. Holler, J. Tschopp, Institute of Biochemistry, University of Lausanne, BIL Research Center, Chemin des Boveresses 155, CH-1066 Epalinges, Switzerland. T. Hunziker, Department of Dermatology, University of Bern, Medical School, CH-3010 Bern, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Wehrli","sequence":"additional","affiliation":[{"name":"I. Viard, P. Wehrli, R. Bullani, D. Salomon, J.-H. Saurat, L. E. French, Department of Dermatology, Geneva University Medical School, CH-1211 Geneva 4, Switzerland. P. Schneider, N. Holler, J. Tschopp, Institute of Biochemistry, University of Lausanne, BIL Research Center, Chemin des Boveresses 155, CH-1066 Epalinges, Switzerland. T. Hunziker, Department of Dermatology, University of Bern, Medical School, CH-3010 Bern, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Bullani","sequence":"additional","affiliation":[{"name":"I. Viard, P. Wehrli, R. Bullani, D. Salomon, J.-H. Saurat, L. E. French, Department of Dermatology, Geneva University Medical School, CH-1211 Geneva 4, Switzerland. P. Schneider, N. Holler, J. Tschopp, Institute of Biochemistry, University of Lausanne, BIL Research Center, Chemin des Boveresses 155, CH-1066 Epalinges, Switzerland. T. Hunziker, Department of Dermatology, University of Bern, Medical School, CH-3010 Bern, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Schneider","sequence":"additional","affiliation":[{"name":"I. Viard, P. Wehrli, R. Bullani, D. Salomon, J.-H. Saurat, L. E. French, Department of Dermatology, Geneva University Medical School, CH-1211 Geneva 4, Switzerland. P. Schneider, N. Holler, J. Tschopp, Institute of Biochemistry, University of Lausanne, BIL Research Center, Chemin des Boveresses 155, CH-1066 Epalinges, Switzerland. T. Hunziker, Department of Dermatology, University of Bern, Medical School, CH-3010 Bern, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nils","family":"Holler","sequence":"additional","affiliation":[{"name":"I. Viard, P. Wehrli, R. Bullani, D. Salomon, J.-H. Saurat, L. E. French, Department of Dermatology, Geneva University Medical School, CH-1211 Geneva 4, Switzerland. P. Schneider, N. Holler, J. Tschopp, Institute of Biochemistry, University of Lausanne, BIL Research Center, Chemin des Boveresses 155, CH-1066 Epalinges, Switzerland. T. Hunziker, Department of Dermatology, University of Bern, Medical School, CH-3010 Bern, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis","family":"Salomon","sequence":"additional","affiliation":[{"name":"I. Viard, P. Wehrli, R. Bullani, D. Salomon, J.-H. Saurat, L. E. French, Department of Dermatology, Geneva University Medical School, CH-1211 Geneva 4, Switzerland. P. Schneider, N. Holler, J. Tschopp, Institute of Biochemistry, University of Lausanne, BIL Research Center, Chemin des Boveresses 155, CH-1066 Epalinges, Switzerland. T. Hunziker, Department of Dermatology, University of Bern, Medical School, CH-3010 Bern, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Hunziker","sequence":"additional","affiliation":[{"name":"I. Viard, P. Wehrli, R. Bullani, D. Salomon, J.-H. Saurat, L. E. French, Department of Dermatology, Geneva University Medical School, CH-1211 Geneva 4, Switzerland. P. Schneider, N. Holler, J. Tschopp, Institute of Biochemistry, University of Lausanne, BIL Research Center, Chemin des Boveresses 155, CH-1066 Epalinges, Switzerland. T. Hunziker, Department of Dermatology, University of Bern, Medical School, CH-3010 Bern, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Hilaire","family":"Saurat","sequence":"additional","affiliation":[{"name":"I. Viard, P. Wehrli, R. Bullani, D. Salomon, J.-H. Saurat, L. E. French, Department of Dermatology, Geneva University Medical School, CH-1211 Geneva 4, Switzerland. P. Schneider, N. Holler, J. Tschopp, Institute of Biochemistry, University of Lausanne, BIL Research Center, Chemin des Boveresses 155, CH-1066 Epalinges, Switzerland. T. Hunziker, Department of Dermatology, University of Bern, Medical School, CH-3010 Bern, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ju\u0308rg","family":"Tschopp","sequence":"additional","affiliation":[{"name":"I. Viard, P. Wehrli, R. Bullani, D. Salomon, J.-H. Saurat, L. E. French, Department of Dermatology, Geneva University Medical School, CH-1211 Geneva 4, Switzerland. P. Schneider, N. Holler, J. Tschopp, Institute of Biochemistry, University of Lausanne, BIL Research Center, Chemin des Boveresses 155, CH-1066 Epalinges, Switzerland. T. Hunziker, Department of Dermatology, University of Bern, Medical School, CH-3010 Bern, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars E.","family":"French","sequence":"additional","affiliation":[{"name":"I. Viard, P. Wehrli, R. Bullani, D. Salomon, J.-H. Saurat, L. E. French, Department of Dermatology, Geneva University Medical School, CH-1211 Geneva 4, Switzerland. P. Schneider, N. Holler, J. Tschopp, Institute of Biochemistry, University of Lausanne, BIL Research Center, Chemin des Boveresses 155, CH-1066 Epalinges, Switzerland. T. Hunziker, Department of Dermatology, University of Bern, Medical School, CH-3010 Bern, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7878463"},{"key":"e_1_3_1_2_3","doi-asserted-by":"crossref","unstructured":"; C. B. Thompson ibid. p. 1456; S. Nagata Cell 88 355 (1997); A. V. Chervonsky et al. ibid. 89 17 (1997).","DOI":"10.1016\/S0092-8674(00)81874-7"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.275.5302.960"},{"key":"e_1_3_1_4_2","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1056\/NEJM199411103311906","volume":"331","author":"Roujeau J. C.","year":"1994","unstructured":"Roujeau J. C., Stern R. S., N. Engl. J. Med. 331, 1272 (1994).","journal-title":"N. Engl. J. Med."},{"key":"e_1_3_1_5_2","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1111\/j.1365-2133.1996.tb06976.x","volume":"134","author":"Paul C.","year":"1996","unstructured":"Paul C., et al., Br. J. Dermatol. 134, 710 (1996).","journal-title":"Br. J. Dermatol."},{"key":"e_1_3_1_6_2","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1001\/archderm.1990.01670250049006","volume":"126","author":"Chan H. L.","year":"1990","unstructured":"Chan H. L., et al., Arch. Dermatol. 126, 43 (1990);","journal-title":"Arch. Dermatol."},{"key":"e_1_3_1_6_3","unstructured":"; J.-C. Roujeau et al. ibid. p. 37; E. Schopf et al. ibid. 127 839 (1991); B. L. Strom et al. ibid. p. 831; H. L. Chan ibid. 131 1212 (1995);"},{"key":"e_1_3_1_6_4","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1016\/0895-4356(96)00035-2","volume":"49","author":"Rzany B.","year":"1996","unstructured":"Rzany B., et al., J. Clin. Epidemiol. 49, 769 (1996).","journal-title":"J. Clin. Epidemiol."},{"key":"e_1_3_1_7_2","unstructured":"TEN was defined as confluent often dark erythema associated with the sudden onset of epidermal detachment mucosal erythema and ulcerations and was always confirmed by a skin biopsy showing full-thickness epidermal necrosis and detachment. In all TEN patients studied (Table 1) the sum of erythematous and detached epidermis was greater or equal to 60% of total body area. Clinical and histological data of each patient was always reviewed in blinded fashion by three separate senior clinicians."},{"key":"e_1_3_1_8_2","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1038\/nm0396-317","volume":"2","author":"Tanaka M.","year":"1996","unstructured":"Tanaka M., et al., Nature Med. 2, 317 (1996).","journal-title":"Nature Med."},{"key":"e_1_3_1_9_2","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1126\/science.274.5291.1363","volume":"274","author":"Hahne M.","year":"1996","unstructured":"Hahne M., et al., Science 274, 1363 (1996).","journal-title":"Science"},{"key":"e_1_3_1_10_2","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/nm0198-031","volume":"4","author":"Tanaka M.","year":"1998","unstructured":"Tanaka M., Itai T., Adachi M., Nagata S., Nature Med. 4, 31 (1998).","journal-title":"Nature Med."},{"key":"e_1_3_1_11_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1084\/jem.187.8.1205","volume":"187","author":"Schneider P.","year":"1998","unstructured":"Schneider P., et al., J. 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U.S.A. 94, 1663 (1997).","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"e_1_3_1_20_2","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1084\/jem.183.2.657","volume":"183","author":"Braun M. Y.","year":"1996","unstructured":"Braun M. Y., Lowin B., French L., Acha-Orbea H., Tschopp J., J. Exp. Med. 183, 657 (1996);","journal-title":"J. Exp. Med."},{"key":"e_1_3_1_20_3","unstructured":"; M. B. Baker N. H. Altman E. R. Podack R. B. Levy ibid. p. 2645; P. R. Galle et al. ibid. 182 1223 (1995);"},{"key":"e_1_3_1_20_4","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1038\/nm0497-409","volume":"3","author":"Kondo T.","year":"1997","unstructured":"Kondo T., Suda T., Fukuyama H., Adachi M., Nagata S., Nature Med. 3, 409 (1997).","journal-title":"Nature Med."},{"key":"e_1_3_1_21_2","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1083\/jcb.133.2.335","volume":"133","author":"French L. E.","year":"1996","unstructured":"French L. E., et al., J. Cell Biol. 133, 335 (1996).","journal-title":"J. Cell Biol."},{"key":"e_1_3_1_22_2","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1038\/nm1296-1361","volume":"2","author":"Strand S.","year":"1996","unstructured":"Strand S., et al., Nature Med. 2, 1361 (1996).","journal-title":"Nature Med."},{"key":"e_1_3_1_23_2","first-page":"2691","volume":"100","author":"Buechner S. A.","year":"1997","unstructured":"Buechner S. A., et al., ibid. 100, 2691 (1997).","journal-title":"ibid."},{"key":"e_1_3_1_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(95)00072-I"},{"key":"e_1_3_1_25_2","doi-asserted-by":"crossref","first-page":"18827","DOI":"10.1074\/jbc.272.30.18827","volume":"272","author":"Schneider P.","year":"1997","unstructured":"Schneider P., et al., J. Biol. Chem. 272, 18827 (1997).","journal-title":"J. Biol. Chem."},{"key":"e_1_3_1_26_2","unstructured":"Serum aliquots from patients with full-blown TEN or MPR and from healthy controls were assessed using a sFasL ELISA kit (Medical & Biological Laboratories Ltd. Nagoya Japan; uses anti-FasL mAb 4H9 and 4A5). TEN was defined as previously described (6). MPR was defined as a drug-related symmetrical confluent cutaneous maculo-papular eruption without clinical signs of epidermal detachment which spontaneously resolved after drug withdrawal. All included cases of MPR had a rash affecting at least 50% of the body surface. Healthy controls were patients less than 40 years of age who were free of cutaneous or systemic disease."},{"key":"e_1_3_1_27_2","unstructured":"Skin biopsies were taken at the time of referral from patients with TEN (at the interface between detached and nondetached skin) MPR (lesional skin) and from healthy controls (non\u2013sun-exposed skin) following informed consent with one part snap-frozen in liquid nitrogen and the other fixed in 4% paraformaldehyde and routinely processed. Immunohistochemistry was performed on cryosections as described (20) using mAb to FasL [A11 Alexis Corp. San Diego CA (8)] mAb to Fas (UB2 Immunotech) and isotype controls."},{"key":"e_1_3_1_28_2","unstructured":"Frozen tissue sections were overlaid with Fas-sensitive Jurkat (human T cell leukemia) cells as described (21 22) with or without preincubation for 30 min with mAb to FasL (NOK1 2.5 \u03bcg\/ml Pharmingen). Jurkat cell apoptosis was determined by flow cytometry using annexin-FITC (Pharmingen) (23)."},{"key":"e_1_3_1_29_2","unstructured":"Cells were preincubated for 24 hours with IVIG (30 mg\/ml; Sando globulin Novartis Bern Switzerland) vehicle [0.9% NaCl and saccharose (51 mg\/ml)] or albumin (30 mg\/ml in 0.9% NaCl) and thereafter susceptibility to rhsFasL was assessed (24)."},{"key":"e_1_3_1_30_2","unstructured":"Equimolar amounts of purified fusion proteins Fas-comp (18) TNFR1-comp or albumin were immunoblotted with either IVIG or monoclonal mouse anti-human Fas antibody (ZB4 Immunotech) and then were revealed by using ECL (Amersham). IVIG did not bind to purified comp alone."},{"key":"e_1_3_1_31_2","unstructured":"We thank G. Radlgruber-Steiger for technical assistance; A. Limat and D. Masson for advice; M. Pech\u00e8re I. Masouy\u00e9 J. Pugin D. Guggisberg and P. de Viragh for data and samples from patients; D. Wohlwend for help with fluorescence-activated cell sorting analysis; N. Fusenig for HaCaT cells; and P. Vassalli for discussions. Supported by grants from the Swiss National Science Foundation (L.E.F. and J.T.) the Ernst Schering Research Foundation the Sir Jules Thorn Charitable Trust the Ernst and Lucie Schmidheiny Foundation the Ligue Genevoise contre le Cancer and the Fondation Medic."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.282.5388.490","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,8]],"date-time":"2024-12-08T13:31:29Z","timestamp":1733664689000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.282.5388.490"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1998,10,16]]},"references-count":40,"journal-issue":{"issue":"5388","published-print":{"date-parts":[[1998,10,16]]}},"alternative-id":["10.1126\/science.282.5388.490"],"URL":"https:\/\/doi.org\/10.1126\/science.282.5388.490","relation":{},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[1998,10,16]]}}}