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Volumn 282, Issue 5388, 1998, Pages 490-493

Inhibition of toxic epidermal necrolysis by blockade of CD95 with human intravenous immunoglobulin

Author keywords

[No Author keywords available]

Indexed keywords

ALLOPURINOL; CARBAMAZEPINE; CEFTRIAXONE; CEFUROXIME; CIPROFLOXACIN; DOXYCYCLINE; FAS ANTIGEN; FAS LIGAND; IBUPROFEN; IMMUNOGLOBULIN; PARACETAMOL; PHENYTOIN;

EID: 0032538505     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.282.5388.490     Document Type: Review
Times cited : (1020)

References (45)
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    • 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.
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    • 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-sun-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.
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    • 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 μg/ml, Pharmingen). Jurkat cell apoptosis was determined by flow cytometry using annexin-FITC (Pharmingen) (23).
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    • 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). 29. Equimolar amounts of purified fusion proteins Fas-comp (18). TNFR1-comp, or albumin were immunoblotted with either IVIG or monoclonal mouse antihuman Fas antibody (ZB4, Immunotech), and then were revealed by using ECL (Amersham). IVIG did not bind to purified comp alone.
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    • note
    • We thank G. Radlgruber-Steiger for technical assistance; A. Limat and D. Masson for advice; M. Pechère, I. Masouyé, 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.


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