title: Recovered patients with Stevens-Johson syndrome and toxic epidermal necrolysis maintain long-lived IFN-γ and sFasL memory response.
abstract: There is evidence that drug-specific T cells are involved in inducing keratinocyte apoptosis in acute stage of Steven-Johson syndrome (SJS) and Toxic epidermal necrolysis (TEN). However, there are few studies that have attempted to examine T cell memory responses over time. We sought to determine the duration of IFN-γ and sFasL memory response to causal drugs in patients with SJS and TEN after remission. Eight patients with previous SJS and TEN were enrolled. Memory T cells were measured by 10-day cultured IFN-γ enzyme-linked immunosorbent spot-forming cell (ELISpot) assay. Effector T-cell responses were measured by ex vivo IFN-γ ELISpot assay and sFasL ELISA. The sFasL-mediated toxicities of drug-stimulated PBMC supernatants against keratinocyte line were further investigated by MTT proliferation assay and Annexin-V staining. We observed significant cultured and ex vivo IFN-γ ELISpot responses against causal drugs in all 8 patients. In addition, the sFasL levels were specifically increased in the supernatant of PBMCs cultured with causal drugs from 6 of 8 patients. Drug-stimulated PBMC supernatants were cytotoxic against keratinocyte line, which was inhibited by anti-FasL mAb in a dose-dependent manner. Our findings confirmed that drug-specific IFN-γ and sFasL memory response against causal drugs could be sustained over several years and further suggest that patients should avoid causal drug re-exposure after the recovery of TEN and SJS.
authors.affiliation: Department of Dermatology, Xijing Hospital, The Fourth Military Medical University, Xi'an, People's Republic of China.
authors.forename: Meng
authors.initials: M
authors.lastname: Fu
authors.forename: Yang
authors.initials: Y
authors.lastname: Gao
authors.forename: Yuefei
authors.initials: Y
authors.lastname: Pan
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Wenjun
authors.initials: W
authors.lastname: Liao
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.forename: Chunying
authors.initials: C
authors.lastname: Li
authors.forename: Chengxin
authors.initials: C
authors.lastname: Li
authors.forename: Tianwen
authors.initials: T
authors.lastname: Gao
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000633:toxicity; D064420:Drug-Related Side Effects and Adverse Reactions; D053222:Fas Ligand Protein / Q000096:biosynthesis* / Q000276:immunology; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D013262:Stevens-Johnson Syndrome / Q000209:etiology / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
chemical_list: D017077:Culture Media, Conditioned; D053222:Fas Ligand Protein; D007371:Interferon-gamma