title: Poor relevance of a lymphocyte proliferation assay in lamotrigine-induced Stevens-Johnson syndrome or toxic epidermal necrolysis.
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
  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.
authors.affiliation: Inserm U 841, Université Paris-Est Créteil, Créteil, France.
authors.forename: Y H
authors.initials: YH
authors.lastname: Tang
authors.forename: M
authors.initials: M
authors.lastname: Mockenhaupt
authors.forename: A
authors.initials: A
authors.lastname: Henry
authors.forename: M
authors.initials: M
authors.lastname: Bounoua
authors.forename: L
authors.initials: L
authors.lastname: Naldi
authors.forename: S
authors.initials: S
authors.lastname: Le Gouvello
authors.forename: A
authors.initials: A
authors.lastname: Bensussan
authors.forename: J C
authors.initials: JC
authors.lastname: Roujeau
mesh_terms: D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects*; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D000077213:Lamotrigine; D008297:Male; D008934:Mitogens / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000494:pharmacology; D012720:Severity of Illness Index; D013262:Stevens-Johnson Syndrome / Q000139:chemically induced* / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D014227:Triazines / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D000927:Anticonvulsants; D008934:Mitogens; D010835:Phytohemagglutinins; D014227:Triazines; D000077213:Lamotrigine