O lúpus eritematoso foi pouco estudado na infância, principalmente nas formas cutânea crônica, subaguda e bolhosa que são infreqüentes nessa faixa etária. Este trabalho tem por objetivo estudar as diversas formas de lúpus eritematoso em crianças. Para tanto, realizamos um estudo retrospectivo por meio da análise de prontuários de pacientes com lúpus eritematoso que teve início até os 16 anos de idade e que foram acompanhados na Divisão de Dermatologia do Hospital das Clínicas da Universidade de São Paulo entre 1991 e 2006. Os pacientes incluídos tiveram o diagnóstico feito pelo quadro clínico e confirmado pela histologia cutânea de uma lesão específica. Foram observados 48 pacientes: 33 com lesões discóides, dois com lúpus profundo, quatro com lúpus eritematoso cutâneo subagudo, quatro com lúpus eritematoso cutâneo agudo sem outras lesões específicas e cinco com lúpus eritematoso bolhoso. Analisadas as características clínicas, laboratoriais, histológicas e de imunofluorescência direta. Dezenove casos preencheram critérios para lúpus eritematoso sistêmico. Houve predomínio discreto no sexo feminino. Casos familiares de lúpus eritematoso estavam presentes em 10% dos pacientes. Vinte e quatro por cento das crianças com lesões discóides preencheram critérios para lúpus eritematoso sistêmico, sendo que 75% apresentavam lesões generalizadas. No lúpus eritematoso sistêmico, as manifestações mais freqüentes foram: cutânea, articular e renal. A glomerulonefrite proliferativa difusa foi a forma mais freqüente de nefrite. Foram observadas alterações hematológicas no limite inferior ou abaixo das taxas relatadas na literatura. Acometimento neurológico ocorreu em 68%. Acometimento cardíaco, pulmonar e do sistema digestivo foram pouco freqüentes. O FAN estava positivo em 95% dos casos e o anticorpo anticardiolipina estava presente em 21%. Dois dos quatro pacientes com lúpus eritematoso cutâneo subagudo preencheram critérios para lúpus eritematoso sistêmico e apresentaram convulsões e nefrite, sendo que um necessitou de transplante renal. Todos referiam fotossensibilidade e o anticorpo anti-Ro estava presente em três dos quatro casos. Todos os pacientes com lúpus eritematoso sistêmico bolhoso preencheram critérios para lúpus eritematoso sistêmico com acometimento renal e baixos níveis de complemento. Nenhum dos dois pacientes com lúpus profundo apresentou critérios para lúpus eritematoso sistêmico. Ambos apresentavam quadro disseminado com histologia típica. O quadro histológico nos demais casos também foi característico e a IgM foi o imunodepósito mais freqüente à imunofluorescência direta. A coloração de PAS (ácido periódico/reagente de Schiff) mostrou espessamento da membrana basal em 37 dos 40 casos estudados. Concluímos que o lúpus eritematoso da infância é semelhante ao do adulto, porém apresenta algumas peculiaridades como menor predomínio no sexo feminino, alta taxa de história familiar de lúpus eritematoso e maior associação com lúpus eritematoso sistêmico nas crianças com lesões discóides. Crianças com lúpus eritematoso cutâneo subagudo e critérios para lúpus eritematoso sistêmico tiveram acometimento sistêmico grave. O acometimento renal foi freqüente nas crianças com lúpus eritematoso sistêmico bolhoso / Lupus erythematosus was not well studied in childhood, especially in its chronic cutaneous, subacute and bullous forms that are uncommon at this age group. The present work aims to study the various forms of childhood lupus erythematosus. We retrospectively studied through medical records patients with lupus erythematosus whose disease had started until 16 years of age who were followed at Dermatology Division of Hospital das Clínicas of University of São Paulo between 1991 and 2006. The patients included had the diagnosis established on clinical grounds and confirmed by histological examination of a specific lesion. We found 48 patients: 33 with discoid lesions, two with lupus profundus, four with subacute cutaneous lupus erythematosus, four with acute cutaneous lupus erythematosus without other specific lesion and five with bullous lupus erythematosus. We analyzed the clinical, laboratorial, histological and direct immunofluorescence findings. Nineteen cases fulfilled the criteria for systemic lupus erythematosus. There was a slight female predominance. Familiar history of lupus erythematosus was present in 10% of cases. Twenty four percent of children with discoid lesions fulfilled the criteria for systemic lupus erythematosus and 75% showed disseminated lesions. The most frequent clinical manifestations in systemic lupus erythematosus were cutaneous, articular and renal. Diffuse proliferative glomerulonephritis was the most frequent form of nephritis. Hematological involvement was bellow or in the bottom of normal limits reported in the literature. Neuropsychiatric disease occurred in 68% of patients. Cardiac, pulmonary and gastrointestinal involvement was not frequent. ANA was positive in 95% of cases and. anticardiolipin antibodies were present in 21%. Two of four subacute cutaneous lupus erythematosus patients fulfilled the criteria for systemic lupus erythematosus and had convulsions and nephritis; one of them was submitted to renal transplantation. All of them referred photosensitivity and anti-Ro was present in three of four cases. All patients with bullous lupus erythematosus fulfilled the criteria for systemic lupus erythematosus and presented renal involvement and low complement levels. None of the two patients with lupus profundus fulfilled the criteria for systemic lupus erythematosus. Both had disseminated lesions and typical histology. Histological examination was also characteristic in the other cases and IgM was the most frequent immunodeposit at direct immunofluorescence. PAS staining showed thickening of basement membrane in 37 of 40 cases studied. To conclude, childhood lupus erythematosus is similar to adult lupus erythematosus, however shows some peculiarities as lower female predominance, high proportion of familiar history of lupus erythematosus and greater association with systemic lupus erythematosus in children with discoid lesions. Children with subacute cutaneous lupus erythematosus and criteria for systemic lupus erythematosus had severe systemic involvement. Renal disease was frequent in children with bullous systemic lupus erythematosus

Introdução: As alopecias cicatriciais são subdivididas em primárias e secundárias. Nas alopecias cicatriciais primárias o folículo piloso é o alvo principal da destruição; diferentemente das secundárias onde a destruição folicular não é o evento patológico primário. Objetivo: Revisar os achados histológicos de pacientes com diagnóstico de alopecia cicatricial primária, em uma fase tardia e reclassificá-los em seus respectivos subtipos. Casuística e Métodos: Os espécimes de biópsia de pacientes com diagnóstico histológico prévio de alopecia cicatricial foram revisados e submetidos a colorações por hematoxilina e eosina (HE), ácido periódico-Schiff (PAS) e Weigert, a fim de reclassificá-los de acordo com os diferentes subtipos de alopecia. Foram utilizados para a revisão histológica critérios de infiltrado inflamatório acrescidos de coloração para fibra elástica. Resultados: Os 37 casos de alopecia cicatricial primária foram reclassificados em: lupus eritematoso discóide (16), líquen plano pilar (4), pseudopelada de Brocq (12), foliculite decalvante (3), foliculite abscedante/dessecante (1), e alopecia não-específica (1). Conclusão: Mesmo em uma fase tardia, pauci ou não inflamatória, o exame histológico, utilizando colorações de rotina, PAS e coloração para fibra elástica, permitiu o diagnóstico mais acurado das alopecias cicatriciais primárias / BACKGROUND: Scarring alopecias are classified into primary and secondary according to the initial site of inflammation. In primary scarring alopecias, the hair follicle is the main target of destruction. The term secondary cicatricial alopecia implies that follicular destruction is not the primary pathologic event. AIMS: To review the histopathologic diagnoses of cases of cicatricial alopecia in order to classify them according to the North American Hair Research Society. PATIENTS AND METHODS: Patients with biopsy specimens diagnosed as cicatricial alopecia seen from 2000 to 2005 at the Dermatologic Department of Hospital das Clínicas, São Paulo University Medical School had hematoxylin and eosin, Periodic Acid-Schiff (PAS) and Weigert stained slides reevaluated and sub-typed into different primary cicatricial alopecias. RESULTS: Thirty-seven cases of primary cicatricial alopecias were reclassified as: discoid lupus erythematosus (16), lichen planus pilaris (4), pseudopelade of Brocq (12), folliculitis decalvans (3), dissecting folliculitis (1), and non-specific scarring alopecia (1). CONCLUSIONS: Even in late, pauci or noninflammatory phases, an approach with systematic evaluation of a constellation of criteria in routine hematoxylin and eosin stain, PAS and Weigert stain permitted an accurate diagnosis of cicatricial alopecias

Introdução: Os anticorpos antiproteína P ribossomal (anti-P) são considerados marcadores sorológicos específicos do Lúpus Eritematoso Sistêmico (LES) e estão associados a acometimento hepático nesta doença. As semelhanças entre a hepatite autoimune (HAI) e a hepatite associada ao LES levou ao questionamento se o anticorpo anti-P também estaria presente na HAI. Objetivo: Avaliar a frequência e significância clínica do anticorpo anti-P em uma grande coorte de pacientes com HAI. Métodos: Foram analisados os soros de 96 pacientes com HAI, coletados no diagnóstico e comparados com 82 soros de indivíduos saudáveis. Todos os soros foram testados para a presença do anticorpo anti-P pelo método de ELISA, do anticorpo anti-DNA de dupla fita pelo método de imunofluorescência indireta usando Crithidia luciliae e do anticorpo anti-Sm pelo método de ELISA. Os critérios de exclusão adotados foram a presença de outros anticorpos específicos de LES como o anti-DNA de dupla fita (n=1) e o anti-Sm (n=2) ou se o paciente apresentasse o diagnóstico de LES definido pelo Colégio Americano de Reumatologia (n=0). Os prontuários médicos foram revisados para dados demográficos, clínicos e resultados de exames laboratoriais relacionados a hepatopatia e anticorpos específicos de HAI. Resultado: Títulos moderados ou alto (> 40 U) de anti-P foram encontrados em 9,7% (9/93) dos pacientes com HAI e em nenhum dos controles (p = 0,003). No diagnóstico, os pacientes com anti-P positivo ou negativo apresentavam características demográficas/clínicas semelhantes, como a frequência de cirrose (44,4% vs 28,5%, p = 0,44) e exames laboratoriais relacionados a hepatite (p > 0,05). Entretanto, ao final do seguimento destes pacientes (média de 10,2 ± 4,9 anos), os pacientes positivos para anticorpos anti-P apresentaram uma maior frequência de cirrose quando comparados a pacientes negativos para anti-P (100% vs 60%, p = 0,04). Conclusão: a demonstração da presença do anticorpo anti-P em pacientes com HAI sem evidência de LES sugere um mecanismo comum de acometimento hepático nestas duas doenças. Além disso, a presença deste anticorpo parece predizer um pior prognóstico nos pacientes com HAI / Background: Autoantibodies to ribosomal P proteins (anti-rib P) are specific serological markers for systemic lupus erythematosus (SLE) and are associated with liver involvement in this disease. The similarity in autoimmune background between autoimmune hepatitis (AIH) and SLE- associated hepatitis raises the possibility that anti-rib P antibodies might also have relevance in AIH. Aims: To evaluate the frequency and clinical significance of anti-rib P antibodies in a large AIH cohort. Methods: Sera obtained at diagnosis of 96 AIH patients and of 82 healthy controls were tested for IgG anti-ribosomal P protein by ELISA. All of the sera were also screened for other lupus-specific autoantibodies, three patients with the presence of anti-dsDNA (n=1) and anti-Sm (n = 2) were excluded. Results: Moderate to high titers (> 40 U) of anti-rib P antibody were found in 9.7% (9/93) of the AIH patients and none of the controls (P = 0.003). At presentation, AIH patients with and without anti-rib P antibodies had similar demographic/clinical features, including the frequency of cirrhosis (44.4% vs. 28.5%, P = 0.44), hepatic laboratorial findings (p > 0.05). Importantly, at the final observation (follow-up period 10.2 ± 4.9 years), the AIH patients with anti-rib P had a significantly higher frequency of cirrhosis compared to the negative group (100% vs. 60%, P = 0.04). Conclusion: The novel demonstration of anti-rib P in AIH patients without clinical or laboratory evidence of SLE suggests a common underlying mechanism targeting the liver in these two diseases. In addition, this antibody appears to predict the patients with worse AIH prognoses

Introdução: Pancreatite é uma manifestação incomum e com risco de vida no lúpus eritematoso sistêmico juvenil (LESJ). Objetivo: Estudar a classificação da pancreatite em pacientes com LESJ de acordo com as definições do Grupo Internacional de Estudos de Pancreatite Pediátrica (INSPPIRE) e determinar prevalência geral, características clínicas, alterações laboratoriais e prognóstico do primeiro episódio. Métodos: Um estudo de coorte retrospectivo multicêntrico incluiu 852 pacientes com LESJ estudados em 10 serviços de referência terciária de reumatologia pediátrica. Resultados: Pancreatite foi diagnosticada em 22 de 852 (2.6%) pacientes com LESJ. Foram classificados como pancreatite aguda em 20 (91%), pancreatite aguda recorrenteem 2 (9%), e nenhum deles apresentou pancreatite crônica. Nenhum deles tinha cálculos biliares, pancreatite traumática, ou relatou o uso de álcool e/ou tabagismo. A comparação dos pacientes com pancreatite (primeiro episódio) e sem esta complicação, revelou uma menor duração da doença [1 (0-10) vs. 4 (0-23) anos, P < 0,0001] e maior mediana do Índice de Atividade de Doença do LES 2000 [21 (0-41) vs. 2 (0-45), P < 0,0001]. A frequência de febre (P < 0,0001), perda de peso (P < 0,0001), serosite (P < 0,0001), nefrite (P < 0,0001), hipertensão arterial (P < 0,0001), insuficiência renal aguda (P < 0,0001), síndrome de ativação macrofágica (P < 0,0001), e morte (P=0,001) foram maiores em pacientes com pancreatite. A freqüência de metilprednisolona endovenosa (P < 0,0001) e a mediana da prednisona [55 (15-60) vs. 11 (1-90) mg/dia, P < 0,0001] foram significantemente maiores em pacientes com pancreatite. Dois pacientes apresentavam pancreatite aguda recorrente com dois episódios distintos, com intervalo sem dor entre os dois episódios de 1 e 4 anos. Conclusão: Este foi o primeiro estudo classificando a pancreatite usando as definições do Grupo Internacional de Estudos de Pancreatite Pediátrica em pacientes com LESJ mostrando uma predominância da pancreatite aguda associado ao tratamento com glicocorticóide e atividade grave da doença / Introduction: Pancreatitis is a rare and a life-threatening systemic lupus erythematosus (SLE) manifestation in childhood-onset SLE (cSLE). Objective: To study the classification of pancreatitis in cSLE according to the International Study Group of Pediatric Pancreatitis and determine the overall prevalence, clinical features, laboratory, and first episode outcomes. Methods: A multicenter cohort study in 10 pediatric rheumatology centers, included 852 patients with cSLE. Results: Pancreatitis was diagnosed in 22 of 852 (2.6%) patients with cSLE. It was classified as acute pancreatitis in 20 (91%), acute recurrent pancreatitis in 2 (9%), and none of them had chronic pancreatitis. None of them had gallstones, traumatic pancreatitis, or reported alcohol/tobacco use. The comparison of patients with pancreatitis (first episode) and without this complication revealed a shorter disease duration [1 (0-10) vs. 4 (0-23) anos, P<0.0001] and higher median of Systemic Lupus Erythematosus Disease Activity Index 2000 [21 (0-41) vs. 2 (0-45), P < 0.0001]. The frequencies of fever (P < 0.0001), weight loss (P < 0.0001), serositis (P < 0.0001), nephritis (P < 0.0001), arterial hypertension (P < 0.0001), acute renal failure (P < 0.0001), macrophage activation syndrome (P < 0.0001), and death (P=0.001) were also higher in patients with pancreatitis. The frequencies of intravenous methylprednisolone use (P < 0.0001) and the median of prednisone dose [55 (15-60) vs. 11 (1-90) mg/dia, P<0.0001] were significantly higher in patients with pancreatitis. Of note, the 2 patients with acute recurrent pancreatitis had 2 episodes, with pain free interval of 1 and 4 years. Conclusions: This was the first study characterizing pancreatitis using the International Study Group of Pediatric Pancreatitis standardized definitions in patients with cSLE showing that the predominant form is acute pancreatitis seen in association with glucocorticoid treatment and active severe disease

Proteinúria é a principal manifestação da nefrite lúpica (NL) e reflete lesão no podócito. Análise dos biomarcadores do podócito foi realizada com o objetivo de identificar se o fenótipo podocitário é distinto na NL membranosa pura e proliferativa. Expressão de sinaptopodina, proteína 1 do tumor de Wilms (Wilms tumor protein 1 - WT1), proteína epitelial glomerular 1 (glomerular epitelial protein 1 - GLEPP1) e nefrina foi avaliada em 52 biópsias de NL por imunohistoquímica. Expressão preservada de sinaptopodina foi observada em apenas 10 (19,2%) de todas as biópsias enquanto que 42 (80,8%) apresentavam expressão reduzida. Ambos os grupos tinham proteinúria semelhante no momento da biópsia (p = 0,22), porém, no seguimento médio de quatro anos houve uma tendência para menores níveis médios de proteinúria nos pacientes com marcação preservada de sinaptopodina (0,26 ± 0,23 vs 0,84 ± 0,90 g/24 h, p = 0,05) do que naqueles com expressão reduzida. Trinta e nove (75%) biópsias foram classificadas como proliferativa e treze (25%) como membranosa pura. Comparação dos biomarcadores do podócito demonstrou predomíno de marcação preservada de sinaptopodina (69,2%), WT1 (69,2%), GLEPP1 (53,9%) e nefrina (60%) no grupo membranosa pura enquanto apenas < 10% das proliferativas apresentaram expressão preservada. Nossos dados sugerem que nas classes proliferativas parece haver lesão estrutural do podócito, enquanto que na membranosa pura o padrão predominantemente preservado sugere uma lesão funcional do podócito que pode ser responsável pelo melhor prognóstico a longo prazo do desfecho da proteinúria / Proteinuria is a major feature of lupus nephritis (LN) and reflects podocyte injury. Analysis of podocyte biomarkers was performed attempting to identify if podocyte phenotype is distinct in pure membranous and proliferative LN. Expression of synaptopodin, Wilms tumor protein 1 (WT1), glomerular epithelial protein 1 (GLEPP1) and nephrin was evaluated in 52 LN biopsies by immunohistochemistry. Preserved synaptopodin expression was observed in only 10 (19,2%) of all biopsies while 42 (80,8%) had a reduced expression. Both groups had comparable proteinuria at the time of biopsy (p=0,22), however, in the mean follow-up of four years there was a tendency to lower mean levels of proteinuria in patients with preserved synaptopodin staining (0,26 ± 0,23 vs. 0,84 ± 0,90 g/24 h, p=0,05) than those with diminished expression. Thirty-nine (75%) biopsies were classified as proliferative and thirteen (25%) as pure membranous. Comparison of podocyte biomarkers demonstrated a predominance of preserved staining of synaptopodin (69,2%), WT1 (69,2%), GLEPP1 (53,9%) and nephrin (60%) in the pure membranous group whereas only < 10% of the proliferative showed preserved expression. Our data suggest that in proliferative forms there seems to occur structural podocyte damage, whereas in the pure membranous the predominant preserved pattern suggests a dysfunctional podocyte lesion that may account for the better long-term prognosis of proteinuria outcome

The purpose of this study was 1) to examine the significance of a patient’s active or passive role in terms of his/her health management; 2) to determine if a relationship exists between one’s active and passive scores and his/her self-directed learning readiness, and 3) to identify if his/her view of one’s self as a patient (when diagnosed with a chronic disease) impacted his/her own personal health management. Utilizing the quantitative analysis of The Self-Directed Learning Readiness Scale and the Vanderbilt Pain Management Inventory, 81 individuals’ descriptive statistics were analyzed. Self-directed learning was found to positively influence an individual’s ability to be an active patient. The moderated demographic characteristics of age, ethnicity, education level, and gender did not have a direct relationship between selfdirected learning readiness and active/passive coping groups. Further, it was established that the majority of the participants within the study, 83.75%, considered themselves an active patient managing their lupus diagnosis. However, 16.25% of the participants did not believe that they were actively managing their illness. Self-directed learning characteristics were examined through the responses to an open-ended question. The two most prevalent themes pertained to active coping and control. Characteristics of self-directed learning readiness appeared predominant amongst the responses, particularly goal-orientation and accepting responsibility for learning. Minimal themes regarding planning and enjoying learning were provided within the data. These characteristics were identified throughout the study in hopes of further research and program implementations that will help to develop leadership abilities and activity levels of self-health management in chronically ill patients. This will enable lupus patients to have a more positive outcome, it will help them successfully manage their own health, and it will improve their overall quality of life. / Includes bibliography. / Dissertation (Ph.D.)--Florida Atlantic University, 2016. / FAU Electronic Theses and Dissertations Collection

This study evaluated two methods for the isolation and purification of anti-DNA antibodies. A two-step affinity purification with streptavidin (SA) biotinylated oligodeoxythymidine (dT) M-280 and protein G Dynabeadsª was compared to a two step method using Melon(TM) Gel and cellulose DNA. Although Melon gel allowed for faster antibody purification and a higher recovery rate it gave a product of less purity than the magnetic bead method. Further characterization of the antibodies was done by PhastGel(TM) non-reducing SDS-PAGE and isoelectric focusing in order to analyze purity and confirm the polyclonal nature of anti-DNA antibodies. Agilent 2100, with a higher resolution then SDS-PAGE, revealed possible subclasses of different MW not detected by SDS-PAGE. ELISA showed that all four IgG antibody subclasses were present, while Western blot confirmed the presence of human IgGs. Ultraviolet spectroscopy, Agilent, and fluorescence based assays were used to demonstrate DNA hydrolytic activity of purified anti-DNA antibody. / by Anna M. Kats. / Thesis (M.S.)--Florida Atlantic University, 2008. / Includes bibliography. / Electronic reproduction. Boca Raton, FL : 2008 Mode of access: World Wide Web.

O lúpus eritematoso sistêmico (LES) é uma doença autoimune e protótipo das doenças por imunocomplexos (IC). A deposição de IC em tecidos ou órgãos leva a um processo inflamatório crônico, que resulta em lesão tecidual. A fisiopatologia deste processo envolve principalmente o sistema do complemento (SC), receptores de IgG (Fc?R), neutrófilos e moléculas de adesão. Os produtos de ativação SC atraem os neutrófilos para o foco inflamatório e sua interação com os IC depositados resulta na liberação de espécies reativas de oxigênio (ERO) e das enzimas dos neutrófilos sobre os tecidos. As ERO podem levar a danos nas estruturas celulares devido ao estresse oxidativo, resultando na exposição de autoantígenos e sustentação da autoimunidade. Várias anormalidades envolvendo neutrófilos, função e expressão dos Fc?R e CR foram descritas no LES. O objetivo deste estudo foi avaliar se essas alterações podem ter implicações para o dano tecidual através do depósito de IC. Devido à importância das interações neutrófilo-endotélio-SC para a inflamação e lesão tecidual por IC no LES, este estudo propôs avaliar o efeito da ativação de neutrófilos e produtos do SC sobre as células endoteliais in vitro. Os resultados mostram que a exposição das células endoteliais aos neutrófilos/LES ativo, sem estímulo, resulta em maior peroxidação lipídica comparada com o controle espontâneo, o que não foi observado com neutrófilos/saudáveis. Contudo, na presença de IC/SHN, a peroxidação lipídica foi maior quando as células endoteliais foram expostas aos neutrófilos/LES inativo comparada ao controle espontâneo. O efeito da ativação dos neutrófilos, em todos os grupos, sobre a peroxidação lipídica das células endoteliais foi dependente da opsonização dos IC pelo complemento (IC/SHN), uma vez que não foi observado quando as proteínas do complemento foram inativadas (IC/SHI). Não houve diferença na produção de ERO entre os neutrófilos dos grupos estudados. Observou-se menor expressão dos Fc?RIIa (CD32) e CR1 em neutrófilos/LES ativo, quando comparados com o grupo controle. Houve maior liberação de catalase pelos neutrófilos/LES, quando estes foram estimulados via Fc?R, e maior produção de glutationa por neutrófilos/LES inativo quando estas células foram estimuladas via Fc?R e CR. A expressão de ICAM-1 não foi diferente entre os grupos de neutrófilos, entretanto foi menor na ausência de complemento. Não houve diferença na medida da ativação da via clássica do complemento avaliada pelo fragmento C4d. Estes resultados mostram que as células endoteliais são mais suscetíveis à peroxidação lipídica na presença de neutrófilos/LES. Contudo, quando o complemento do soro é inativado, esta suscetibilidade desaparece, bem como há menor liberação de ICAM-1 por todos os grupos de neutrófilos e maior liberação de catalase por neutrófilos/LES. A interação dos neutrófilos/LES com células endoteliais pode ser deletéria para este último e depender da atividade das proteínas do sistema complemento. O modelo desenvolvido neste estudo pode contribuir para a compreensão do envolvimento dos neutrófilos e do SC nas lesões teciduais no LES. / Systemic lupus erythematosus (SLE) is an autoimmune disease and prototype of immune complex diseases (IC). The deposition of IC in tissues or organs leads to a chronic inflammatory process, which results in tissue injury. The pathophysiology of this process mainly involves the complement system (SC), IgG (Fc?R) receptors, neutrophils and adhesion molecules. SC activation products attract neutrophils to the inflammatory focus and their interaction with deposited IC results in the release of reactive oxygen species (ROS) and neutrophil enzymes into tissues. ROS can lead to damage to cell structures due to oxidative stress, resulting in the exposure of autoantigens and the support of autoimmunity. Several abnormalities involving neutrophils, function and expression of Fc?R and CR have been described in SLE. The aim of this study was to assess whether these changes may have implications for tissue damage through the deposition of IC. Due to the importance of neutrophil-endothelial-SC interactions for inflammation and tissue damage by IC in SLE, this study proposed to evaluate the effect of the activation of neutrophils and SC products on endothelial cells in vitro. The results show that exposure of endothelial cells to active neutrophils / SLE without stimulus results in higher lipid peroxidation compared to spontaneous control, which was not observed with neutrophils / healthy. However, in the presence of IC / complement from normal human serum (NHS), lipid peroxidation was greater when endothelial cells were exposed to inactive neutrophils / SLE compared to spontaneous control. The effect of neutrophil activation in all groups on endothelial cell lipid peroxidation was dependent on IC with complement (IC / NHS), as it was not observed when complement proteins were inactivated (IC / INHS). There was no difference in ROS production among the neutrophils of the studied groups. Lower expression of Fc?RIIa (CD32) and CR1 in active neutrophils / SLE, when compared with the control group, was observed. There was greater release of catalase by neutrophils / SLE, when they were stimulated via Fc?R, and increased production of glutathione by neutrophils / inactive SLE when these cells were stimulated via Fc?R and CR. There was no difference in expression of ICAM-1 between the neutrophil groups, however it was lower in the absence of complement. There was no difference in the extent of the activation of the classical complement pathway evaluated by the C4d fragment. These results show that endothelial cells are more susceptible to lipid peroxidation in the presence of neutrophils / SLE. However, when serum complement is inactivated, this susceptibility disappears, as well as there is a lower release of ICAM-1 by all neutrophil groups and greater release of catalase by neutrophils / SLE. The interaction of neutrophils / SLE with endothelial cells may be deleterious to the latter and depends on the activity of the complement system proteins. The model developed in this study may contribute to the understanding of neutrophil and SC involvement in tissue lesions in SLE.

[pt] Focalizando o Lúpus Eritematoso Sistêmico como uma doença psicossomática, localizada no limiar entre o psíquico e o físico, esta dissertação pretende contribuir para o estudo do trauma, da dor psíquica e física, utilizando-se das teorias de Winnicott e Freud para este fim. Considerando que a dor física faz parte do quadro clínico do Lúpus Eritematoso Sistêmico, este trabalho levanta a questão de que o quadro álgico torna-se muitas vezes insuportável, por se somar à dor física, o eu que dói, decorrente de traumas vividos. O corpo adoecido e dolorido reclama a ausência de um meio ambiente bom o bastante levando a quebra na vivência de continuidade do ser, (Winnicott), assim como a ausência de uma barreira de estímulos (Freud) forte, que permita o desenvolvimento adequado do eu. Para ilustrar as idéias apresentadas no trabalho, foram retirados fragmentos dos relatos, realizados no ambulatório do Hospital Universitário Pedro Ernesto. / [en] Focusing Systemic Erythematosus as a psychosomatic disease, located in the difficult thesrhold between the psychic and the physical, this dissertation intends to contribute for the study of the trauma, of psychic and physical pain, using the theories of Winnicott and Freud for this purpose. Considering that physical pain is part of the clinical picture of Systemic Lupus Erythematosus, this work raises the subject that of pain becomes many times unbearable, considering that to physical pain, pain of the self is odded, due to past, experienced traumas. The sick and aching body claims the break in the experience of the continuity of being, lock of a good enough environment (Winnicott), as well as lock of a strong stimuli barrier (Freud), allowing for on appropriate development of the self. To illustrate the ideas presented in this work, fragments of patients reports from the clinic of the University Hospital, Pedro Ernesto, were used for this purpose.

Background: Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease characterised by autoantibody production and variable clinical features, ranging from mild to severe disease. Patients with SLE are at increased risk of developing accelerated atherosclerosis. Biomarkers have potential utility in SLE as markers of disease or predictors of future clinical events and mortality. Objective The aim of this thesis was to identify serological biomarkers predictive for erosive arthritis (EA), cardiovascular events (CVEs), mortality and subclinical atherosclerosis in SLE. Methods: In chapters 2 to 4, study subjects were SLE patients from Bath. Anti-cyclic citrullinated peptide antibodies (ACPA) and HLA-DR and -DQ were studied for markers of EA, and anticardiolipin (aCL) and lipoprotein profiles for markers of CVEs and mortality. In chapters 5 and 6, study subjects were women with SLE from Manchester. B-mode ultrasound scans of subjects' carotid arteries were performed at baseline and follow-up time-points to detect atherosclerotic plaque. Baseline IgG and IgM antiphospholipid (aPL) antibodies and CV risk factors were studied for markers of subclinical atherosclerosis. Clinical data collected for all studies included SLE features and auto-antibody profiles. Results: ACPA was identified as a marker of a SLE phenotype with EA - "rhupus". Patients with major erosive arthritis were HLA-DQB1*0302 carriers. Increased aCL GPL levels and total cholesterol : high density lipoprotein-C (TC : HDL-C) ratio were markers for future CVEs, and increased TC : HDL ratio, aCL GPL and lipoprotein(a) concentrations were markers for increased mortality. Lower HDL-C concentrations and anti-annexin A5 (anti-AnxA5) GPL were markers of carotid plaque progression. Conclusion: This thesis identified new markers for EA, subclinical atherosclerosis and future CVE and mortality risk in SLE. Strategies to incorporate these new CV markers into clinical CV risk assessments may assist in distinguishing the subset of SLE patients most at risk of developing accelerated atherosclerosis.