Diss. (sammanfattning) Stockholm : Karol. inst., 1999. / Härtill 6 uppsatser.

Habilitationsschrift--Marburg. / "Literatur-Verzeichnis": p. 58.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 6 uppsatser.

Introdução: lúpus eritematoso é uma doença crônica auto-imune que afeta o tecido conjuntivo e múltiplos órgãos. Manifestações orais são pouco freqüentes, caracterizadas por lesões de aspectos variados. Diagnósticos diferenciais incluem líquen plano, leucoplasia, eritema polimorfo e pênfigo vulgar. Métodos: O objetivo deste trabalho foi estudar as lesões orais de 46 doentes com LE do ambulatório de Colagenoses e de Estomatologia do HC-FMUSP, enfocando os aspectos clínicos, histológicos, a proliferação e maturação epitelial (expressão de citoqueratinas, p-53 e ki-67), as proteínas da membrana basal (colágeno IV, fibronectina e laminina) e a constituição do infiltrado inflamatório (anticorpos CD3, CD4, CD8, CD 20, CD 68 e CD1A). Resultados: Quarenta e seis doentes (34 mulheres e 12 homens) apresentaram lesões orais, todos com alterações histológicas de mucosite de interface, infiltrado inflamatório superficial e profundo e depósitos subepiteliais PAS positivos. Positividade para IgM ao longo da membrana basal do epitélio foi observada pelo exame de IFD na maioria dos doentes. A avaliação das citoqueratinas mostrou um epitélio hiperproliferativo com expressão de CK 5/6 e CK 14 em todas as camadas, além da marcação do p-53 e ki-67 na camada basal. Os linfócitos T subtipo CD4 predominaram no infiltrado inflamatório, sendo mais rara a presença de linfócitos B e macrófagos. Células de Langerhans foram ausentes. Colágeno IV mostrou intensa expressão na membrana basal, a expressão da fibronectina foi mais difusa na lâmina própria e não se observou a presença de laminina. Conclusão: as lesões orais do LE predominam no sexo feminino e exibem aspectos clínicos variados. A mucosa jugal e lábios foram mais afetados. O aspecto histológico foi o de mucosite de interface associada a infiltrado inflamatório superficial e profundo com predomínio de linfócitos T CD4+, As citoqueratinas mostraram alteração no padrão de distribuição, caracterizando um epitélio hiperproliferativo. Na matriz extracelular predominou o colágeno IV na membrana basal. / Background: Lupus erythematosus (LE) is a multifactorial autoimmune disease of unknown cause. It may affect the oral mucosa in either its acute, subacute and chronic forms, with varied prevalence. Reports evaluate that mucosal involvement ranges from 9-45% in patients with systemic disease and from 3-20% in patients with chronic cutaneous involvement. Methods: Forty-six patients with confirmed diagnosis of LE, presenting oral lesions were included in the study. Oral mucosal lesions were analyzed clinically and their histopathological features were investigated. Additionally, using immunohistochemistry, the status of epithelial maturation proliferation and apoptosis of the biopsied lesions was assessed through the expression of cytokeratins, ki-67 and Fas. The inflammatory infiltrate constitution was also assessed using immunohistochemistry against the following clusters of differentiation: CD3, CD4, CD8, CD20, CD68 and CD1A. Finally, the components of extracellular matrix were analyzed trough the expression of collagen, laminin and fibronectina. Results: From 46 (15,45%) patients with specific LE oral lesions 34 were females (25) with cutaneous LE and 9 with systemic LE) and 12 were males (11 with cutaneous LE and 1 with systemic LE) out of 298 patients examined with lupus erithematosus. Clinical aspects of lesions varied, and lips and buccal mucosa were the most affected sites. Histologically, lesions revealed lichenoid mucositis with perivascular infiltrate and thickening of basement membrane. Cytokeratins profile showed hyperproliferative epithelium, with expression of CK5/6 and CK14 on all epithelial layers, CK16 on all suprabasal layers. CK10 was verified on the prickle cell layer only. Ki-67 and p53 were sparsely positive and Fas was present both in the basal layer of the epithelium and in the inflammatory infiltrate. Inflammatory infiltrate was predominantly composed by T lymphocytes of the CD4 subtype, with a minor prevalence of Blymphocytes, isolated macrophages and rare Langerhans cells. Matrix proteins collagen IV and laminin were present mainly in the basement membranes of the epithelium and blood vessels, whilst fibronectina was not detected. Conclusions: Oral lesions of lupus erythematosus show a variety of clinical aspects and histologically consist of a lichenoid mucositis with deep inflammatory infiltrate. Patterns of cytokeratins expression are of a hyperproliferative epithelium and the inflammatory infiltrate is composed predominantly of T-lymphocytes positive lymphocytes. This panel must analyzed in relation to the inflammatory cytokines for a better understanding of the mechanisms of the disease.

Introdução: lúpus eritematoso é uma doença crônica auto-imune que afeta o tecido conjuntivo e múltiplos órgãos. Manifestações orais são pouco freqüentes, caracterizadas por lesões de aspectos variados. Diagnósticos diferenciais incluem líquen plano, leucoplasia, eritema polimorfo e pênfigo vulgar. Métodos: O objetivo deste trabalho foi estudar as lesões orais de 46 doentes com LE do ambulatório de Colagenoses e de Estomatologia do HC-FMUSP, enfocando os aspectos clínicos, histológicos, a proliferação e maturação epitelial (expressão de citoqueratinas, p-53 e ki-67), as proteínas da membrana basal (colágeno IV, fibronectina e laminina) e a constituição do infiltrado inflamatório (anticorpos CD3, CD4, CD8, CD 20, CD 68 e CD1A). Resultados: Quarenta e seis doentes (34 mulheres e 12 homens) apresentaram lesões orais, todos com alterações histológicas de mucosite de interface, infiltrado inflamatório superficial e profundo e depósitos subepiteliais PAS positivos. Positividade para IgM ao longo da membrana basal do epitélio foi observada pelo exame de IFD na maioria dos doentes. A avaliação das citoqueratinas mostrou um epitélio hiperproliferativo com expressão de CK 5/6 e CK 14 em todas as camadas, além da marcação do p-53 e ki-67 na camada basal. Os linfócitos T subtipo CD4 predominaram no infiltrado inflamatório, sendo mais rara a presença de linfócitos B e macrófagos. Células de Langerhans foram ausentes. Colágeno IV mostrou intensa expressão na membrana basal, a expressão da fibronectina foi mais difusa na lâmina própria e não se observou a presença de laminina. Conclusão: as lesões orais do LE predominam no sexo feminino e exibem aspectos clínicos variados. A mucosa jugal e lábios foram mais afetados. O aspecto histológico foi o de mucosite de interface associada a infiltrado inflamatório superficial e profundo com predomínio de linfócitos T CD4+, As citoqueratinas mostraram alteração no padrão de distribuição, caracterizando um epitélio hiperproliferativo. Na matriz extracelular predominou o colágeno IV na membrana basal. / Background: Lupus erythematosus (LE) is a multifactorial autoimmune disease of unknown cause. It may affect the oral mucosa in either its acute, subacute and chronic forms, with varied prevalence. Reports evaluate that mucosal involvement ranges from 9-45% in patients with systemic disease and from 3-20% in patients with chronic cutaneous involvement. Methods: Forty-six patients with confirmed diagnosis of LE, presenting oral lesions were included in the study. Oral mucosal lesions were analyzed clinically and their histopathological features were investigated. Additionally, using immunohistochemistry, the status of epithelial maturation proliferation and apoptosis of the biopsied lesions was assessed through the expression of cytokeratins, ki-67 and Fas. The inflammatory infiltrate constitution was also assessed using immunohistochemistry against the following clusters of differentiation: CD3, CD4, CD8, CD20, CD68 and CD1A. Finally, the components of extracellular matrix were analyzed trough the expression of collagen, laminin and fibronectina. Results: From 46 (15,45%) patients with specific LE oral lesions 34 were females (25) with cutaneous LE and 9 with systemic LE) and 12 were males (11 with cutaneous LE and 1 with systemic LE) out of 298 patients examined with lupus erithematosus. Clinical aspects of lesions varied, and lips and buccal mucosa were the most affected sites. Histologically, lesions revealed lichenoid mucositis with perivascular infiltrate and thickening of basement membrane. Cytokeratins profile showed hyperproliferative epithelium, with expression of CK5/6 and CK14 on all epithelial layers, CK16 on all suprabasal layers. CK10 was verified on the prickle cell layer only. Ki-67 and p53 were sparsely positive and Fas was present both in the basal layer of the epithelium and in the inflammatory infiltrate. Inflammatory infiltrate was predominantly composed by T lymphocytes of the CD4 subtype, with a minor prevalence of Blymphocytes, isolated macrophages and rare Langerhans cells. Matrix proteins collagen IV and laminin were present mainly in the basement membranes of the epithelium and blood vessels, whilst fibronectina was not detected. Conclusions: Oral lesions of lupus erythematosus show a variety of clinical aspects and histologically consist of a lichenoid mucositis with deep inflammatory infiltrate. Patterns of cytokeratins expression are of a hyperproliferative epithelium and the inflammatory infiltrate is composed predominantly of T-lymphocytes positive lymphocytes. This panel must analyzed in relation to the inflammatory cytokines for a better understanding of the mechanisms of the disease.