Diss. (sammanfattning) Stockholm : Karolinska institutet, 2010.

Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Patients were selected for the study on the basis of 1: A diagnosis of systemic Lupus Erythematosus according to the 1982 revised American Rheumatology Association criteria47 and 2: An adequate biopsy defined as containing at least six glomeruli. Patients were biopsied at Groote Schuur Hospital during the period 1978 to 1988 and the indications for renal biopsy were clinical based on laboratory results of renal function. Patients were followed between 1 and 120 months with a mean observation period of 34 months. The clinical records were scrutinised and the following pa·rameters were noted at the time of biopsy: age, sex, race, time from diagnosis to biopsy, serum urea, creatinine, creatinine clearence and urinary 24 hour protein. Using the latest serum urea, creatinine, creatinine clearence and / or 24 hour urinary protein where available, outcome was graded as: 1: An improvement in renal function 2: A stable renal function 3: Deterioration in renal function 4: Patient on dialysis 5: Death due to disease.

Thesis (M.Sc.)--Memorial University of Newfoundland, Faculty of Medicine, 1999. / Typescript. Bibliography: leaves 113-124.

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: O Lúpus eritematoso sistêmico (LES) é uma doença inflamatória autoimune crônica de etiologia ainda pouco conhecida, e de natureza pleomórfica, que intercala períodos de atividade e remissão. O desenvolvimento da autoimunidade no LES está associado à perda da tolerância imunológica e do controle imunorregulatório, tendo seus achados clínicos e laboratoriais variados. A atividade do LES pode ser medida pelo SLEDAI (systemic lupus erythematosus disease activity index) que é uma ferramenta complexa e que exige treinamento e conhecimento para sua aplicação. O volume plaquetário médio (VPM) é um marcador de ativação de plaquetas associado à inflamação, o que o torna um potencial candidato para a avaliação de atividade de doença no LES. Objetivos: Avaliar o VPM em pacientes com LES e comparar com indivíduos hígidos. Estudar a correlação entre o VPM e o índice de atividade de doença (SLEDAI) nos pacientes com LES. Analisar a correlação entre o VPM e a velocidade de sedimentação globular (VSG), a proteína C reativa (PCR), e os componentes do complemento C3 e C4 Métodos: Estudo transversal no qual foram incluídos 81 pacientes com LES segundo critérios de classificação diagnóstica do American College of Rheumatology (ACR), e 58 controles hígidos. Os pacientes foram selecionados consecutivamente por conveniência, de acordo com exames laboratoriais e SLEDAI devidamente calculados. As coletas foram realizadas entre outubro de 2015 e julho de 2016. LES ativo foi definido como SLEDAI>0 no momento da coleta. O VPM foi analisado no equipamento de automação Sysmex XE 5000. Resultados: O VPM estava reduzido nos pacientes com LES em atividade, quando comparado ao grupo de pacientes com LES inativo (10,0±0,7fL vs. 10,7±1,0fL, p=0,005). Existe uma fraca correlação inversa entre o valor do SLEDAI e o VPM (r=-0,29, p=0,009). Houve uma diferença significativa no VPM entre o grupo dos controles e os pacientes com LES ativo / Background Systemic Lupus Erythematosus (SLE) is an inflammatory autoimmune chronic disease etiology still unknown, and pleomorphic nature, which intersperses periods of activity and remission. The development of autoimmunity in SLE is related to loss of immunological tolerance and immunoregulatory control and clinical symptoms can be varied. The SLE activity can be measured by SLEDAI (systemic lupus erythematosus disease activity) which is a complex tool and it requires time and knowledge for your application. The MPV (mean platelet volume) is a marker of platelet activation and has been shown to be associated with inflammation, which makes it a potential candidate for use in the assessment of disease activity in SLE. In this study, we evaluated the MPV (Mean platelet volume) in healthy individuals and compared with SLE patients and correlate with SLEDAI VPM. Objectives: -To evaluate the MPV in SLE patients and compared with healthy individuals; to study the correlation between MPV and the SLEDAI patients with SLE and assess a possible correlation between MPV with erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), complement 3 (C3), and complement 4 (C4) Methods: This is a cross-sectional study in which 81 patients with SLE according to the American College of Rheumatology (ACR) diagnostic classification criteria and 58 healthy controls were included. Patients were selected for convenience, according to laboratory tests and SLEDAI duly calculated. The collections were carried out between October 2015 and July 2016. Active LES was defined as SLEDAI>0 at the time of collection. The VPM was analyzed in the Sysmex XE 5000 automation equipment. Results: In this study in patients with active SLE, the MPV is reduced when compared to the group of patients with inactive SLE [10.0±0.7fL vs. 10.7±1.0fL, p=0.005]. There is a weak inverse correlation between the SLEDAI value and the MPV (r=-0.29, p=0.009). There was a significant difference between the control group and the patients with active SLE (10.9 ±1.0fL vs. 10.0±0.7fL, p <0.001). In contrast, the MPV was similar between the control group and the group of patients with inactive SLE (10.9±1.0fLvs10.7±1.0fL, p=0.40). There was no correlation between MVP and CRP, ESR, C3 and C4. Conclusion: MPV is decreased in patients with active SLE and inversely correlated with SLEDAI. Despite the difference between MVP values, between active and inactive SLE patients, the results may not be clinically relevant. Prospective longitudinal studies are needed to better characterize the fluctuation of MPV in different states of disease activity to more clearly define the role of MPV in SLE.

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.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.

Introdução: O Lúpus eritematoso sistêmico (LES) é uma doença inflamatória autoimune crônica de etiologia ainda pouco conhecida, e de natureza pleomórfica, que intercala períodos de atividade e remissão. O desenvolvimento da autoimunidade no LES está associado à perda da tolerância imunológica e do controle imunorregulatório, tendo seus achados clínicos e laboratoriais variados. A atividade do LES pode ser medida pelo SLEDAI (systemic lupus erythematosus disease activity index) que é uma ferramenta complexa e que exige treinamento e conhecimento para sua aplicação. O volume plaquetário médio (VPM) é um marcador de ativação de plaquetas associado à inflamação, o que o torna um potencial candidato para a avaliação de atividade de doença no LES. Objetivos: Avaliar o VPM em pacientes com LES e comparar com indivíduos hígidos. Estudar a correlação entre o VPM e o índice de atividade de doença (SLEDAI) nos pacientes com LES. Analisar a correlação entre o VPM e a velocidade de sedimentação globular (VSG), a proteína C reativa (PCR), e os componentes do complemento C3 e C4 Métodos: Estudo transversal no qual foram incluídos 81 pacientes com LES segundo critérios de classificação diagnóstica do American College of Rheumatology (ACR), e 58 controles hígidos. Os pacientes foram selecionados consecutivamente por conveniência, de acordo com exames laboratoriais e SLEDAI devidamente calculados. As coletas foram realizadas entre outubro de 2015 e julho de 2016. LES ativo foi definido como SLEDAI>0 no momento da coleta. O VPM foi analisado no equipamento de automação Sysmex XE 5000. Resultados: O VPM estava reduzido nos pacientes com LES em atividade, quando comparado ao grupo de pacientes com LES inativo (10,0±0,7fL vs. 10,7±1,0fL, p=0,005). Existe uma fraca correlação inversa entre o valor do SLEDAI e o VPM (r=-0,29, p=0,009). Houve uma diferença significativa no VPM entre o grupo dos controles e os pacientes com LES ativo / Background Systemic Lupus Erythematosus (SLE) is an inflammatory autoimmune chronic disease etiology still unknown, and pleomorphic nature, which intersperses periods of activity and remission. The development of autoimmunity in SLE is related to loss of immunological tolerance and immunoregulatory control and clinical symptoms can be varied. The SLE activity can be measured by SLEDAI (systemic lupus erythematosus disease activity) which is a complex tool and it requires time and knowledge for your application. The MPV (mean platelet volume) is a marker of platelet activation and has been shown to be associated with inflammation, which makes it a potential candidate for use in the assessment of disease activity in SLE. In this study, we evaluated the MPV (Mean platelet volume) in healthy individuals and compared with SLE patients and correlate with SLEDAI VPM. Objectives: -To evaluate the MPV in SLE patients and compared with healthy individuals; to study the correlation between MPV and the SLEDAI patients with SLE and assess a possible correlation between MPV with erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), complement 3 (C3), and complement 4 (C4) Methods: This is a cross-sectional study in which 81 patients with SLE according to the American College of Rheumatology (ACR) diagnostic classification criteria and 58 healthy controls were included. Patients were selected for convenience, according to laboratory tests and SLEDAI duly calculated. The collections were carried out between October 2015 and July 2016. Active LES was defined as SLEDAI>0 at the time of collection. The VPM was analyzed in the Sysmex XE 5000 automation equipment. Results: In this study in patients with active SLE, the MPV is reduced when compared to the group of patients with inactive SLE [10.0±0.7fL vs. 10.7±1.0fL, p=0.005]. There is a weak inverse correlation between the SLEDAI value and the MPV (r=-0.29, p=0.009). There was a significant difference between the control group and the patients with active SLE (10.9 ±1.0fL vs. 10.0±0.7fL, p <0.001). In contrast, the MPV was similar between the control group and the group of patients with inactive SLE (10.9±1.0fLvs10.7±1.0fL, p=0.40). There was no correlation between MVP and CRP, ESR, C3 and C4. Conclusion: MPV is decreased in patients with active SLE and inversely correlated with SLEDAI. Despite the difference between MVP values, between active and inactive SLE patients, the results may not be clinically relevant. Prospective longitudinal studies are needed to better characterize the fluctuation of MPV in different states of disease activity to more clearly define the role of MPV in SLE.

Introdução: O Lúpus eritematoso sistêmico (LES) é uma doença inflamatória autoimune crônica de etiologia ainda pouco conhecida, e de natureza pleomórfica, que intercala períodos de atividade e remissão. O desenvolvimento da autoimunidade no LES está associado à perda da tolerância imunológica e do controle imunorregulatório, tendo seus achados clínicos e laboratoriais variados. A atividade do LES pode ser medida pelo SLEDAI (systemic lupus erythematosus disease activity index) que é uma ferramenta complexa e que exige treinamento e conhecimento para sua aplicação. O volume plaquetário médio (VPM) é um marcador de ativação de plaquetas associado à inflamação, o que o torna um potencial candidato para a avaliação de atividade de doença no LES. Objetivos: Avaliar o VPM em pacientes com LES e comparar com indivíduos hígidos. Estudar a correlação entre o VPM e o índice de atividade de doença (SLEDAI) nos pacientes com LES. Analisar a correlação entre o VPM e a velocidade de sedimentação globular (VSG), a proteína C reativa (PCR), e os componentes do complemento C3 e C4 Métodos: Estudo transversal no qual foram incluídos 81 pacientes com LES segundo critérios de classificação diagnóstica do American College of Rheumatology (ACR), e 58 controles hígidos. Os pacientes foram selecionados consecutivamente por conveniência, de acordo com exames laboratoriais e SLEDAI devidamente calculados. As coletas foram realizadas entre outubro de 2015 e julho de 2016. LES ativo foi definido como SLEDAI>0 no momento da coleta. O VPM foi analisado no equipamento de automação Sysmex XE 5000. Resultados: O VPM estava reduzido nos pacientes com LES em atividade, quando comparado ao grupo de pacientes com LES inativo (10,0±0,7fL vs. 10,7±1,0fL, p=0,005). Existe uma fraca correlação inversa entre o valor do SLEDAI e o VPM (r=-0,29, p=0,009). Houve uma diferença significativa no VPM entre o grupo dos controles e os pacientes com LES ativo / Background Systemic Lupus Erythematosus (SLE) is an inflammatory autoimmune chronic disease etiology still unknown, and pleomorphic nature, which intersperses periods of activity and remission. The development of autoimmunity in SLE is related to loss of immunological tolerance and immunoregulatory control and clinical symptoms can be varied. The SLE activity can be measured by SLEDAI (systemic lupus erythematosus disease activity) which is a complex tool and it requires time and knowledge for your application. The MPV (mean platelet volume) is a marker of platelet activation and has been shown to be associated with inflammation, which makes it a potential candidate for use in the assessment of disease activity in SLE. In this study, we evaluated the MPV (Mean platelet volume) in healthy individuals and compared with SLE patients and correlate with SLEDAI VPM. Objectives: -To evaluate the MPV in SLE patients and compared with healthy individuals; to study the correlation between MPV and the SLEDAI patients with SLE and assess a possible correlation between MPV with erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), complement 3 (C3), and complement 4 (C4) Methods: This is a cross-sectional study in which 81 patients with SLE according to the American College of Rheumatology (ACR) diagnostic classification criteria and 58 healthy controls were included. Patients were selected for convenience, according to laboratory tests and SLEDAI duly calculated. The collections were carried out between October 2015 and July 2016. Active LES was defined as SLEDAI>0 at the time of collection. The VPM was analyzed in the Sysmex XE 5000 automation equipment. Results: In this study in patients with active SLE, the MPV is reduced when compared to the group of patients with inactive SLE [10.0±0.7fL vs. 10.7±1.0fL, p=0.005]. There is a weak inverse correlation between the SLEDAI value and the MPV (r=-0.29, p=0.009). There was a significant difference between the control group and the patients with active SLE (10.9 ±1.0fL vs. 10.0±0.7fL, p <0.001). In contrast, the MPV was similar between the control group and the group of patients with inactive SLE (10.9±1.0fLvs10.7±1.0fL, p=0.40). There was no correlation between MVP and CRP, ESR, C3 and C4. Conclusion: MPV is decreased in patients with active SLE and inversely correlated with SLEDAI. Despite the difference between MVP values, between active and inactive SLE patients, the results may not be clinically relevant. Prospective longitudinal studies are needed to better characterize the fluctuation of MPV in different states of disease activity to more clearly define the role of MPV in SLE.