title: IL-4, IL-5, TGF-beta1 and IFN-gamma mRNAs detected by a new in situ amplification system in cicatricial pemphigoid.
abstract: The process that induces chronic progressive scarring in cicatricial pemphigoid (CP), a rare group of autoimmune mucocutaneous blistering diseases, is still under investigation. The tendency to heal with scar formation observed in CP could be due to the specific localization of the antigen in the basement membrane zone or could depend on the frequent recurrence of the disease in a localized area. The release of soluble fibrogenic factors by inflammatory infiltrating cells has also been considered as pathogenetically relevant. The aim of this study is to evaluate the expression of mRNA for IL-4, IL-5, TGF-beta1, IFN-gamma in patients with CP, and investigate the role of the cytokine profile as a possible cause of the clinical features and course of the disease. Fourteen patients (3 male, 11 female; age range 40-72 years) with oral (n = 10), preputial (n = 3) and cutaneous (n = 1) CP were studied. The formalin-fixed and paraffin-embedded biopsies were examined by in situ hybridization performing a new amplification system based on biotinyl-tyramide. As a control, 4 patients (2 male, 2 female; age range 58-73 years) affected by bullous pemphigoid (BP), the most common autoimmune subepidermal blistering disease, were also examined. In CP, IL-4 mRNA expression was present in 4 out of the 14 cases analysed. IL-5 was detected in 12 CP biopsies. TGF-beta1 and IFN-gamma mRNAs were identified in 9 and 11 CP cases, respectively. In BP, an IL-4 hybridization signal could not be observed in any of the cases. By contrast IL-5, TGF-beta1 and IFN-gamma mRNA analyses were positive in all four BP cases. Our results suggest the presence of a T-cell population with a mixed cytokine pattern in the cellular infiltrate of both blistering diseases, with a corresponding increase of Th2-like activity in fully developed lesions, irrespective of the different sites involved. In addition, on the basis of the constant presence of TGF-beta1 mRNA in the different lesional phases of CP, and its overlapping expression in BP, we hypothesize that the involvement of additional factors is responsible for the scarring course typical of CP.
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D016207:Cytokines / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D006801:Humans; D017403:In Situ Hybridization; D007371:Interferon-gamma / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D015848:Interleukin-5 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010390:Pemphigoid, Benign Mucous Membrane / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D010391:Pemphigoid, Bullous / Q000235:genetics / Q000276:immunology / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000235:genetics; D053773:Transforming Growth Factor beta1
chemical_list: D016207:Cytokines; D015848:Interleukin-5; D012333:RNA, Messenger; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D015847:Interleukin-4; D007371:Interferon-gamma