title: The CD40/CD40 ligand system is expressed in the cutaneous lesions of erythema multiforme and Stevens-Johnson syndrome/toxic epidermal necrolysis spectrum.
abstract: BACKGROUND
  Erythema multiforme (EM) and Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) are determined by a dysregulation of cellular immunity.
  
  
  OBJECTIVE
  To evaluate the effector role of cellular immunity and the involvement of the CD40/CD40 ligand (CD40L) system in the pathogenesis of EM and SJS/TEN.
  
  
  METHODS
  Biopsy specimens from eight patients with EM and six with SJS/TEN were stained for immunohistochemical examination using the alkaline phosphatase/antialkaline phosphatase method. The monoclonal antibodies used included those to CD1a, CD4, CD8, CD40, CD40L, CD68, Fas, Fas ligand (FasL) and myeloperoxidase.
  
  
  RESULTS
  The cellular infiltrate in both EM and SJS/TEN lesions was composed mainly of T lymphocytes and CD68+ macrophages. We also detected large amounts of neutrophils. Fas and FasL were very highly expressed in SJS and TEN, but weakly in EM. CD40 staining was strong in all tissue sections; there were numerous CD40L+ cells in SJS/TEN but much fewer in EM.
  
  
  CONCLUSIONS
  Activated T lymphocytes and macrophages, but also neutrophils, are presumably the main triggers of mucocutaneous damage in the SJS/TEN disease spectrum. The Fas/FasL system is significantly expressed in SJS/TEN lesions, but not in EM, where this apoptotic pathway presumably does not play a pivotal role in the epidermal damage. We suggest that the CD40/CD40L system may represent an important pathway of induction of SJS/TEN lesions, while in EM it would contribute to the immunoinflammation only as a second-line mechanism.
authors.affiliation: Istituto Dermopatico dell'Immacolata, IRCCS, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Caproni
authors.forename: D
authors.initials: D
authors.lastname: Torchia
authors.forename: E
authors.initials: E
authors.lastname: Schincaglia
authors.forename: W
authors.initials: W
authors.lastname: Volpi
authors.forename: A
authors.initials: A
authors.lastname: Frezzolini
authors.forename: D
authors.initials: D
authors.lastname: Schena
authors.forename: A
authors.initials: A
authors.lastname: Marzano
authors.forename: P
authors.initials: P
authors.lastname: Quaglino
authors.forename: C
authors.initials: C
authors.lastname: De Simone
authors.forename: A
authors.initials: A
authors.lastname: Parodi
authors.forename: E
authors.initials: E
authors.lastname: Barletta
authors.forename: P
authors.initials: P
authors.lastname: Fabbri
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D019013:CD40 Antigens / Q000378:metabolism*; D023201:CD40 Ligand / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology; D004892:Erythema Multiforme / Q000276:immunology*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D016130:Immunophenotyping; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D012867:Skin / Q000276:immunology*; D013262:Stevens-Johnson Syndrome / Q000276:immunology*
chemical_list: D019013:CD40 Antigens; D023201:CD40 Ligand