Poor relevance of a lymphocyte proliferation assay in lamotrigine-induced Stevens-Johnson syndrome or toxic epidermal necrolysis

Clin Exp Allergy. 2012 Feb;42(2):248-54. doi: 10.1111/j.1365-2222.2011.03875.x. Epub 2011 Oct 6.

Abstract

Background: Prior use of 'lymphocyte transformation test' (LTT) in Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) provided conflicting results, possibly dependent on sampling dates (acute vs. late).

Objective: Evaluation of LTT in patients with SJS or TEN who reacted to lamotrigine (LTG). In a small subgroup we explored the possible role of regulatory T cells (T-reg).

Methods: Acute phase samples (9) and post-recovery samples (14) from cases of SJS or TEN to LTG were provided by the RegiSCAR-study group. Controls were persons never exposed to LTG (12), patients exposed without reaction (6), and patients who developed a mild eruption to LTG (6). LTT was performed by measuring (3) H-thymidine incorporation after 3 days of incubation with phytohemmaglutinin, LTG (10 μg/mL) or medium. Stimulation index ≥ 2 was considered positive. In 16 cases LTT was redone after depletion of T-reg by fluorescence activated cell sorting.

Results: Positive LTT was observed in 3/6 cases of mild eruptions, 1/9 SJS/TEN-cases tested during the acute phase and 3/14 SJS/TEN-cases tested after recovery. We noted a very mild and nonsignificant trend for an increased response after depletion of T-reg in late samples from SJS or TEN patients.

Conclusions and clinical relevance: With the largest number of LTT performed in patients with SJS or TEN to a single drug, we confirmed that reactive cells are rarely detected in these reactions. Poor reactivity did not seem related to T-reg. Other in vitro assays than those testing proliferation should be evaluated, before raising the hypothesis that specific cells disappeared by undergoing apoptosis during the reaction.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticonvulsants / administration & dosage
  • Anticonvulsants / adverse effects*
  • Apoptosis / drug effects
  • Apoptosis / immunology
  • Cell Proliferation / drug effects*
  • Cells, Cultured
  • Female
  • Humans
  • Lamotrigine
  • Male
  • Mitogens / pharmacology
  • Phytohemagglutinins / pharmacology
  • Severity of Illness Index
  • Stevens-Johnson Syndrome / chemically induced*
  • Stevens-Johnson Syndrome / immunology*
  • Stevens-Johnson Syndrome / metabolism
  • Stevens-Johnson Syndrome / pathology
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism
  • T-Lymphocytes, Regulatory / pathology
  • Triazines / administration & dosage
  • Triazines / adverse effects*

Substances

  • Anticonvulsants
  • Mitogens
  • Phytohemagglutinins
  • Triazines
  • Lamotrigine