Recovered patients with Stevens-Johson syndrome and toxic epidermal necrolysis maintain long-lived IFN-γ and sFasL memory response

PLoS One. 2012;7(9):e45516. doi: 10.1371/journal.pone.0045516. Epub 2012 Sep 18.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis / drug effects
  • Apoptosis / immunology
  • Cell Line
  • Cells, Cultured
  • Culture Media, Conditioned / toxicity
  • Drug-Related Side Effects and Adverse Reactions
  • Fas Ligand Protein / biosynthesis*
  • Fas Ligand Protein / immunology
  • Female
  • Humans
  • Immunologic Memory*
  • Interferon-gamma / biosynthesis*
  • Interferon-gamma / metabolism
  • Keratinocytes / drug effects
  • Keratinocytes / metabolism
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Middle Aged
  • Stevens-Johnson Syndrome / etiology
  • Stevens-Johnson Syndrome / immunology*
  • Stevens-Johnson Syndrome / metabolism
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Young Adult

Substances

  • Culture Media, Conditioned
  • Fas Ligand Protein
  • Interferon-gamma

Grants and funding

This study was supported by the Key Science and Technology Program of Shaanxi Province, China (2011K12-03-07) and by Program for Young Talents in Fourth Military Medical University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.