Background: Erythema multiforme (EM) and Stevens-Joh- nson syndrome (SJS)/toxic epidermal necrolysis (TEN) are determined by a dysregulation of cellular immunity. Objectives: To evaluate the effector role of cellular ...Background: Erythema multiforme (EM) and Stevens-Joh- nson syndrome (SJS)/toxic epidermal necrolysis (TEN) are determined by a dysregulation of cellular immunity. Objectives: 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.展开更多
Background: There have been only two reports on immunophenotypic characteriza tion in the cutaneous lesions of dermatomyositis (DM) that emphasize the importa nce of the infiltrating CD4+ T lymphocytes. Objectives: To...Background: There have been only two reports on immunophenotypic characteriza tion in the cutaneous lesions of dermatomyositis (DM) that emphasize the importa nce of the infiltrating CD4+ T lymphocytes. Objectives: To characterize the imm unophenotype of the cells that infiltrate the lesional skin of DM and to evaluat e the possible T-helper (Th) polarization Th1/Th2 through detection of specifi c cytokines, chemokine receptors and markers of cellular activation. Methods: Sk in biopsy specimens derived from pathognomonic lesions (Gottron’s papules and Gottron’s sign) of eight patients withDMwere immunostainedwith a large panel o fmonoclonal antibodies to CD3, CD4, CD8, myeloperoxidase(MPO), eosinophil cation ic protein, tryptase, CD40, CD40 ligand (CD40L), HLA-DR, interleukin (IL)- 2, IL- 4, IL- 5, IL- 13, interferon-γ , tumour necrosis factor-α , recept or 3 for CXC chemokines (CXCR3) and receptor 3 for CC chemokines, using the alka line phosphatase-antialkaline phosphatase method. Control specimens were obtai ned from five healthy subjects and from six patients with discoid lupus erythema tosus. Results: Activated CD4+ Th lymphocytes (HLA-DR+ CD40L+ ) were the principal infiltrating cells in the lesional skin of DM; the CD4/CD8 ratio was a pproximately 2· 5. A mixed Th1/Th2 profile and higher Th1 cytokine production t ogether with significant staining for CXCR3 were detected. Neutrophil granulocyt es were the second most abundant population; eosinophil granulocytes were very p oorly represented. Conclusions: Activated CD4+ T cells presumably mediate the main pathogenetic mechanisms in pathognomonic skin lesions. The interaction betw een CD40 andCD40L could be an important mecha nismof cellular activation in cutaneous immune-mediated inflammation by ind uction of secretion of proinflammatory cytokines and chemokines. Neither Th1 nor Th2 clear polarization was found, although there was a slight Th1 prevalence. T here was a significant quantity of MPO+ cells (neutrophil granulocytes) in the in-flamed tissue, and they might have a role in sustaining the chronic inflam mation.展开更多
文摘Background: Erythema multiforme (EM) and Stevens-Joh- nson syndrome (SJS)/toxic epidermal necrolysis (TEN) are determined by a dysregulation of cellular immunity. Objectives: 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.
文摘Background: There have been only two reports on immunophenotypic characteriza tion in the cutaneous lesions of dermatomyositis (DM) that emphasize the importa nce of the infiltrating CD4+ T lymphocytes. Objectives: To characterize the imm unophenotype of the cells that infiltrate the lesional skin of DM and to evaluat e the possible T-helper (Th) polarization Th1/Th2 through detection of specifi c cytokines, chemokine receptors and markers of cellular activation. Methods: Sk in biopsy specimens derived from pathognomonic lesions (Gottron’s papules and Gottron’s sign) of eight patients withDMwere immunostainedwith a large panel o fmonoclonal antibodies to CD3, CD4, CD8, myeloperoxidase(MPO), eosinophil cation ic protein, tryptase, CD40, CD40 ligand (CD40L), HLA-DR, interleukin (IL)- 2, IL- 4, IL- 5, IL- 13, interferon-γ , tumour necrosis factor-α , recept or 3 for CXC chemokines (CXCR3) and receptor 3 for CC chemokines, using the alka line phosphatase-antialkaline phosphatase method. Control specimens were obtai ned from five healthy subjects and from six patients with discoid lupus erythema tosus. Results: Activated CD4+ Th lymphocytes (HLA-DR+ CD40L+ ) were the principal infiltrating cells in the lesional skin of DM; the CD4/CD8 ratio was a pproximately 2· 5. A mixed Th1/Th2 profile and higher Th1 cytokine production t ogether with significant staining for CXCR3 were detected. Neutrophil granulocyt es were the second most abundant population; eosinophil granulocytes were very p oorly represented. Conclusions: Activated CD4+ T cells presumably mediate the main pathogenetic mechanisms in pathognomonic skin lesions. The interaction betw een CD40 andCD40L could be an important mecha nismof cellular activation in cutaneous immune-mediated inflammation by ind uction of secretion of proinflammatory cytokines and chemokines. Neither Th1 nor Th2 clear polarization was found, although there was a slight Th1 prevalence. T here was a significant quantity of MPO+ cells (neutrophil granulocytes) in the in-flamed tissue, and they might have a role in sustaining the chronic inflam mation.
