Orientador: Simone Appenzeller / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-23T19:14:15Z (GMT). No. of bitstreams: 1 Pereira_KarinaDanielle_M.pdf: 1028779 bytes, checksum: 901fb7a5f4993b6c8133e68fb9913463 (MD5) Previous issue date: 2013 / Resumo: Lúpus Eritematoso Sistêmico (LES) é uma doença crônica, autoimune e multissistêmica, caracterizada por períodos de atividade e remissão, que apresenta maior prevalência no sexo feminino, habitualmente durante o período reprodutivo. Assim, o interesse em identificar fatores que se correlacionem à saúde reprodutiva nessas pacientes tem sido crescente. Objetivo: Avaliar a saúde reprodutiva, em mulheres com LES e mulheres sem histórico de doença autoimune. Elucidar o papel da atividade e dano da doença, ansiedade e depressão, qualidade de vida e imagem corporal na saúde reprodutiva de mulheres com LES. Método: Foram selecionados pacientes consecutivos com LES acompanhadas na Unidade de Reumatologia da UNICAMP entre 2011/2012. Avaliação da saúde sexual e reprodutiva (SPEQ), atividade da doença (SLEDAI), dano cumulativo (SDI), transtornos de humor (BAI, BDI), avaliação da qualidade de vida (SF-36) e questões sobre imagem corporal (BCQ) foram realizadas. Resultados: Duzentos e sessenta e oito pacientes e 132 controles foram incluídas na pesquisa. Mulheres com LES apresentaram pior saúde reprodutiva que mulheres sadias (p<0,05), 49,25% das pacientes e 15,15% das controles não faziam uso de qualquer método contraceptivo (p=0,01), disfunção sexual foi observado em 80,9% das pacientes e em 20,41% das controles (p=0,01). Presença de transtornos do humor (ansiedade e depressão) (p=0,01), fadiga (p=0,01), piora da imagem corporal (p=0,02), e baixa qualidade de vida (p=0,03), foram significativamente mais frequentes em mulheres com LES quando comparadas a mulheres saudáveis. Observamos uma associação entre pior saúde reprodutiva e ansiedade (p=0,001), fadiga (p=0,001) e baixa qualidade de vida (p=0,002). Conclusão: Aspectos relacionados à saúde reprodutiva necessitam de uma atenção especial dos profissionais e devem ser abordados rotineiramente, propiciando melhor qualidade de vida das pacientes e de seus parceiros, melhorando assim o impacto da doença / Abstract: Systemic lupus erythematous (SLE) is a chronic, multisystem autoimmune and characterized by periods of activity and remission, which is more prevalent in women, usually during the reproductive period. Thus, the interest in identifying factors that correlate reproductive health in these patients has been increasing. Objective: To assess reproductive health in women with SLE and women without a history of autoimmune disease, unrelated, and elucidate its association with disease activity and damage, anxiety and depression, quality of life and body image. Methods: We selected consecutive patients with SLE followed in the Rheumatology Unit of Campinas between 2011/2012. Assessment of sexual and reproductive health (SPEQ), disease activity (SLEDAI), cumulative damage (SDI), mood disorders (BAI, BDI), assessment of quality of life (SF36) and questions about body image (BCQ) were performed. Two hundred and sixty-eight patients and 132 controls were included in the survey. Results: Women with SLE had poorer reproductive health healthy women (p <0.05), 49.25% of patients and 15.15% of controls were not using any method of contraception (p=0.01), sexual dysfunction was observed in 80.9% of patients and 20.41% of the controls (p=0.01). Presence of mood disorders (anxiety and depression) (p=0.01), fatigue (p=0.01), worsening of body image (p=0.02), and low quality of life (p=0.03), were significantly more prevalent in SLE patients compared to healthy women. We observed an association between poor reproductive health and anxiety (p= 0,001), fatigue (p= 0.001) and poor quality of life (p= 0.002). Conclusion: Aspects related to reproductive health require special attention from professionals and should be addressed routinely providing better quality of life for patients and their partners, thus enhancing the impact of the disease / Mestrado / Clinica Medica / Mestra em Clínica Médica

Orientador: Elemir Macedo de Souza / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-18T22:06:21Z (GMT). No. of bitstreams: 1 Franca_AndreaFernandesEloydaCosta_D.pdf: 3442848 bytes, checksum: 1ed0dba42432e3b03b1b7c6c386bdf41 (MD5) Previous issue date: 2011 / Resumo: O lúpus eritematoso (LE) é uma doença auto-imune com espectro clínico variado. O lúpus eritematoso cutâneo (LEC) inclui o lúpus eritematoso agudo (LECA), o subagudo (LECSA) e o crônico (LECC). Lesões acrômicas podem ocorrer durante a evolução do LE, embora nunca tenham sido estudadas histologicamente. O objetivo deste trabalho é descrever os achados clínicos, laboratoriais e histológicos das lesões acrômicas no LE. Foram selecionados 12 pacientes com LE de um grupo de 220 atendidos no período de 2005 a 2008, sendo sete com LECC e cinco com LECSA. Doze pacientes com vitiligo e 10 controles de pele sã foram usados para comparação. As alterações histológicas encontradas foram: infiltrado inflamatório (75%); hiperceratose e espessamento da zona da membrana basal (ZMB) (66,7%); retificação da epiderme (58,3%); ceratinócitos apoptóticos epidérmicos, elastose e telangectasias (50%); fibrose (41,7%); degeneração vacuolar da ZMB (33,3%); rolhas córneas (16,7%). O diagnóstico histológico de LE foi possível em quatro casos. Melanina pela coloração de Fontana Masson (FM) foi vista em cinco casos e incontinência pigmentar em quatro. Melanócitos foram evidenciados em amostras de cinco doentes através da reação imunohistoquímica pelo HMB45 e Melan-A, com diferença estatística em relação aos controles. Quando comparado ao vitiligo, a diferença foi estatisticamente significante para os achados histológicos: ceratinócitos apoptóticos epidérmicos (p=0,014), espessamento da ZMB (p=0,009) e fibrose (p=0,037). Em relação à quantificação dos melanócitos, não houve diferença estatística entre o grupo LE e vitiligo usando os anticorpos Melan-A e HMB45. Concluímos que as lesões acrômicas no LE correspondem a lesões residuais, decorrentes de processo inflamatório liquenóide prévio que destrói os melanócitos. Não é possível diferenciar as lesões vitiligóides das duas dermatoses pela presença ou ausência de melanócitos, embora a repigmentação seja possível em ambas as doenças devido a presença de melanogênese ativa comprovada pela positividade pelo HMB45 / Abstract: Lupus Erythematosus (LE) is an autoimmune disorder with multiple clinical manifestations. Skin damage is a hallmark of the disease. Cutaneous LE (CLE) includes acute LE (ACLE), subacute LE (SCLE) and chronic LE (CCLE). Although achromic lesions are often found in patients with LEC, there are no detailed data about the histological features of such lesions. Therefore, we designed this study to determine clinical, laboratorial and histological profile of patients with LEC presenting achromic lesions. Between 2005 and 2008, we identified 12 individuals with LEC and acromic lesions from a larger group of 220 patients with LEC that were followed at the Dermatology outpatient clinic. There were seven patients with LECC and five with LECSA. Twelve patients with chronic stable vitiligo and 10 controls of unaffected skin were used for comparison. The most frequent histological abnormalities found in LEC-related achromic lesions were inflammatory infiltrates (75%); hyperkeratosis and thickening of the basement membrane (BM) (66.7%); epidermal flattening (58.3%); apoptotic epidermal keratinocytes, elastosis and vasodilation (50%); fibrosis (41.7%); hydropic degeneration of the basal cells (33.3%); follicular plugging (16.7%). These achromic lesions retained histological features that enabled the diagnosis of CLE to be established in four patients. Fontana Masson (FM) staining was positive for melanin in five cases and revealed pigmentary incontinence in four. Immunohistochemistry for HMB45 and Melan-A identified melanocytes in five CLE-related achromic lesions. Melanocyte counts were significantly smaller in achromic lesions when compared to unaffected skin samples. When compared to vitiligo, CLE-related achromic lesions showed more frequently apoptotic epidermal keratinocytes (p=0,014), thickening of the BM (p=0,009) and fibrosis (p=0,037). Melanocyte counts according to immunohistochemistry were similar in CLE and vitiligo groups. Our results indicate that CLE-related achromic lesions represent residual scars due to chronic lichenoid inflammation that leads to melanocyte destruction. Melanocyte count does not help to distinguish CLE-related achromic lesions and true vitiligo lesions. Despite this, HMB45 staining was sometimes positive in both conditions, which indicates active melanogenesis and suggests that repigmentation may be possible at least for some individuals / Doutorado / Clinica Medica / Doutor em Clínica Médica

Orientador: Simone Appenzeller / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-19T11:05:02Z (GMT). No. of bitstreams: 1 Aldar_Henrique_M.pdf: 1202072 bytes, checksum: f32d5c89beb6e8a3a6884266359ea535 (MD5) Previous issue date: 2011 / Resumo: O Lúpus Eritematoso Sistêmico Juvenil (LESJ) é uma doença inflamatória crônica, de etiologia desconhecida e natureza autoimune com início até os 16 anos de idade. O comprometimento do sistema nervoso central (SNC) é difícil de ser avaliado no LESJ. Os anticorpos anti-P ribossomal são autoanticorpos dirigidos contra epítopos de fosfoproteínas do complexo ribonucleoproteico ribossomal e com maior prevalência em pacientes com até 18 anos de idade. A proteína S100? tem baixo peso molecular, sendo composta de 91 aminoácidos e localizada principalmente nas células da neuroglia, células de Schwann e na maioria dos nervos sensoriais do tronco cerebral. Os objetivos deste trabalho foram determinar a associação entre anticorpos anti-P ribossomal e a proteína S100? com manifestações clínicas e laboratoriais no LESJ; avaliar a prevalência dos anticorpos anti-P ribossomal em pacientes com LESJ, familiares de primeiro grau e indivíduos controles saudáveis; e avaliar os níveis de proteína S100? em pacientes com LESJ e indivíduos controles saudáveis. Foram selecionados pacientes consecutivos com LESJ acompanhados na Reumatologia Pediátrica da Universidade Estadual de Campinas entre 2009/2010. Familiares aparentados em primeiro grau com os pacientes também foram incluídos. Os indivíduos do grupo controle foram pareados por idade, sexo e antecedentes demográficos. Manifestações clínicas, laboratoriais, atividade da doença [SLE Disease Activity Index (SLEDAI)], dano cumulativo [Lupus International Collaborating Clinics / American College of Rheumatology Damage Index (SDI)] e medicação em uso foram avaliados. Incluímos 50 pacientes com LESJ (média de idade de 16,82 ± 3,46 anos), 35 familiares (média de idade de 38,73 ± 3,89 anos), e 20 controles saudáveis (média de idade de 18,3 ± 4,97 anos). Observamos os anticorpos anti-P ribossomal em 13 (26%) dos pacientes com LESJ, e em nenhum familiar (p<0,01) ou controle (p<0,01). A presença dos anticorpos anti-P ribossomal esteve associada à presença de ansiedade no LESJ (p<0,002). Pacientes com distúrbio cognitivo (mediana=38,08) apresentaram níveis de S100? significativamente maiores quando comparados aos pacientes sem distúrbio cognitivo (mediana=16,12; p=0,01) e indivíduos controles (mediana=23,62; p<0,05). Nenhuma outra manifestação clínica, laboratorial, e de tratamento esteve associada com o anticorpo anti-P ribossomal ou com a proteína S100? no LESJ. A partir destes dados concluímos que os anticorpos anti-P ribossomal são frequentemente observados em pacientes com LESJ e estiveram associados com a presença de ansiedade neste grupo de pacientes; e que a presença de distúrbio cognitivo esteve associada com níveis elevados de S100?, indicando a presença de lesão neuronal nestes pacientes / Abstract: Childhood-onset systemic lupus erythematosus (cSLE) is a chronic inflammatory disease of unknown etiology and autoimmune nature, with disease onset until 16 years of age. It is difficult to assess the central nervous system involvement in cSLE. The antiribosomal P antibodies are autoantibodies directed against epitopes of ribosomal phosphoproteins from the ribonucleoprotein complex and more frequently observed in patients with up to 18 years old. The S100? protein has a low molecular weight, being composed of 91 amino acids and mainly located in the cells of the neuroglia, Schwann cells and sensory nerves in most of the brainstem. Our objectives were to determine the association between antiribosomal P antibodies and S100? protein with clinical and laboratory manifestations in cSLE; to assess the prevalence of antiribosomal P antibodies in patients with cSLE, first-degree relatives and healthy control subjects; and to evaluate S100? protein levels in cSLE patients and healthy control subjects. Consecutive cSLE patients followed in Pediatric Rheumatology at the University of Campinas between 2009/2010 were selected for this study. First-degree relatives were also included in this work. The control group was matched for age, gender and demographic background. Clinical, laboratory, disease activity [SLE Disease Activity Index (SLEDAI)], cumulative damage [Systemic Lupus International Collaborating Clinics /American College of Rheumatology Damage Index (SDI)] and medication in use were assessed. Fifty cSLE patients, (mean age of 16.82 ± 3.46 years), 35 relatives (mean age of 38.73 ± 3.89 years) and 20 healthy controls (mean age 18.3 ± 4.97 years) were selected. Thirteen (26%) cSLE patients presented the antiribosomal P antibodies, no first-degree relative (p<0.01) or control (p<0.01) presented antiribosomal P antibodies. Antiribosomal P antibodies were associated to anxiety in this cohort of cSLE patients (p<0.02). Patients with cognitive impairment (median = 38.08) had significantly higher levels of S100? compared to patients without cognitive impairment (median = 16.12, p = 0.001) and controls (median = 23.62, p <0.05 ).No other clinical, laboratory, and treatment were associated with the antiribosomal P antibodies or S100? protein in cSLE. These data shows that the antiribosomal P antibodies are often observed in cSLE patients and that it was associated with the presence of anxiety in this group of patients. The presence of cognitive impairment was associated with elevated levels of S100?, suggesting neuronal damage in these patients / Mestrado / Ciencias Basicas / Mestre em Clinica Medica

A method for assaying poly (ADP-ribose) polymerase (PADPRP) activity in lymphocytes of systemic lupus erythematosus (SLE) patients has been developed. Using this method, PADPRP activity has been studied in lymphocytes from 15 patients and 13 controls. The mean activity in SLE lymphocytes was significantly lower than that in controls and 60% of the SLE patients demonstrated activities below the minimum of the control population. Possible mechanisms for this altered metabolism were investigated. The Km app of PADPRP for NAD; size distribution, branch frequency, and rates of turnover of polymers; competition for substrate; and number of PADPRP molecules were studied. The data demonstrated that SLE lymphocytes have a decreased synthetic capacity rather than alterations in the substrate or in turnover of the product.

Bakgrund: Systemisk lupus erythematosus (SLE) är en kronisk autoimmun sjukdom som angriper friska celler, vävnader och organ. Varför patienter får SLE är ännu inte helt klarlagt. Det finns inget botemedel mot sjukdomen och den är svår att diagnostisera. Det finns endast medicin som används för att lindra symtom. Syfte: Syftet med litteraturstudien var att belysa patienters upplevelser av att leva med SLE. Metod: Litteraturstudien utgick från en induktiv ansats, kritisk granskning och genomgång av artiklar. Databaserna som användes var CINAHL, PubMed och PsycInfo. Resultat: Resultatet av studien mynnade ut i fyra olika kategorier: upplevelser av fysiska begränsningar, upplevelser av psykiska begränsningar, upplevelser av begränsningar och möjligheter i det sociala livet samt upplevelser av ekonomiska problem. Patienterna upplevde svårigheter vid fysisk aktivitet på grund av smärta. De upplevde psykiska problem som depression och ångest. Relationsproblem och ekonomiska problem uppkom även. Slutsats: Patienter med SLE är i behov av stöd som gör att de kan ta sig genom sin dag lättare då patienterna upplever att sjukdomen påverkar kroppen negativt. Mer utbildning behövs för sjuksköterskestudenter och personal för att lättare förstå patientens upplevelser och utforma omvårdnadsåtgärder därefter. / Background: Systemic lupus erythematosus is a chronic autoimmune disease which attacks healthy cells, tissues and organs. Why patients get SLE is not yet 100% clear. There's no cure for SLE and it's hard to diagnose. Only treatment for relief the symptoms are available. Aim: The aim of this study was to investigate patients´ experience of living with SLE. Method: The method used in this study was a structured literature review with an inductive approach and a clear view of audited articles. The databases used in this study were CINAHL, PubMed and PsycInfo. Result: The result of this study was divided into four groups: Experiences of physical limitations, experiences of psychic limitations, experiences of limitations and benefits in social life and experiences of economic limitations. The patients experienced difficulties with pain which affected all the physical activities. The patients experienced psychic problems. Depression and anxiety was a big problem. The patients also experienced relationship problems and economic problems. Conclusion: Patients with SLE is in need of support because they experience that the illness affects the body in a negative way. More education for nursing students and personnel is necessary to understand patient experiences of SLE and form care measures.

Introduction: SLE is associated with pro-atherogenic metabolic derangement and an elevated cardiovascular risk. The vascular endothelium may be a key interface between active SLE and premature atherosclerosis. Improved understanding of the contribution of inflammation and its management to cardiovascular risk in SLE will inform personalised treatment decisions in SLE patients. Methods: Data from an international inception cohort was used to investigate the relationship between inflammatory disease activity, lupus phenotype and corticosteroid exposure and the metabolic syndrome (MetS) over 2 years in SLE patients. The relationship between disease activity (BILAG-2004) and markers of endothelial function (flow-mediated dilatation (FMD) of the brachial artery) and endothelial damage (endothelial microparticles (EMPs)) following a change in anti-inflammatory therapy was investigated in a longitudinal cohort of patients with active SLE. Results: MetS was common in young SLE patients (12.6-16.0%) over the initial 2 years of disease. Factors independently associated with developing MetS over the 2-year study period were (odds ratio (95% CI)) Hispanic ethnicity (3.47 (1.76, 6.86)), higher initial peak corticosteroid dose (1.02 (1.01,1.03)), and elevated anti-dsDNA antibodies at study entry (1.86(1.19,2.81)). MetS was often persistent and preceding MetS strongly predicted future MetS (4.83 (2.93, 7.87)). Patients with active SLE had reduced FMD (median (IQR) FMD 1.63% (-1.22, 5.32) vs. 5.40% (3.02, 8.57); p = 0.05) and elevated EMPs (157,548/ml (59,906, 272,643) vs. 41,025 (30,179, 98,082); p = 0.003) compared to age-matched controls. Both improved following a change in anti-inflammatory therapy, and correlated moderately with change in disease activity over time. Conclusions: Inflammatory disease activity and higher doses of corticosteroids in very early disease influence the development of MetS in SLE, which can become persistent. Endothelial dysfunction is common in patients with active SLE but can be improved with better disease control. Therefore even from disease onset, therapeutic regimes should be individually tailored to achieve good disease control whilst minimising corticosteroid doses, to improve cardiovascular risk surrogates in SLE.

No description available.

Bakgrund: Systemisk lupus erythematosus (SLE) är en sjukdom som varierar i uttryck och allvarlighetsgrad och involverar hantering av många utmanande aspekter vilket kan leda till fysiska och psykologiska konsekvenser och begränsa förmågan att fungera fullt ut i det dagliga livet. Syfte: Syftet var att belysa personers upplevelser av att leva med systemisk lupus erythematosus i det dagliga livet. Metod: En litteraturöversikt med kvalitativ metod utfördes med induktiv ansats baserad på 13 vetenskapliga originalartiklar som analyserades enligt Graneheim och Lundmans innehållsanalys. Resultat: Personerna med SLE upplevde känslomässiga besvär som oro, depression och självmordstankar. De upplevde begränsningar i det dagliga livet, minskad självständighet och de lärde sig leva med sjukdomen på olika sätt. Relationer påverkades, det var en börda att förklara sjukdomen, de önskade förståelse, bekräftelse och att få stöd var betydelsefullt. Diskussion: Fynden i resultatet visar vikten av att använda en personcentrerad omvårdnad utifrån tidigare kunskap, erfarenheter och känsla av sammanhang (KASAM) vilket kan underlätta att hantera de negativa konsekvenserna av att leva med SLE, då personen blir bekräftad, förstådd och får omvårdnad efter behov, värderingar och önskemål. Slutsats: Litteraturöversikten bidrar till bättre förutsättningar i omvårdnaden då den tillför ökad kunskap och förståelse om upplevelsen av att leva med SLE. Det behövs ytterligare forskning i omvårdnad med fokus på fördjupad förståelse och kunskap om de varierande negativa konsekvenserna och vilka behov som sjukdomen SLE medför, och belysa vikten av att använda personcentrerad omvårdnad för att främja hälsa och lindra lidandet. / <p>Examinationsdatum: 2020-11-03</p>

Gain-of-function polymorphisms in the gene encoding human interferon regulatory factor-5 (IRF5) are associated with an increase in risk for the development of the autoimmune disease Systemic Lupus Erythematosus (SLE). IRF5 is a transcription factor that participates in the activation of the immune system through its role in both innate and adaptive immune cells. To determine the role of IRF5 in lupus pathogenesis in vivo, we evaluated the effect of Irf5-deficiency in the MRL/lpr mouse lupus model. We find that Irf5-deficient (Irf5-/-) MRL/lpr mice develop much less severe disease than their Irf5-sufficient (Irf5+/+) littermates, demonstrating an important role for IRF5 in disease pathogenesis in vivo. Patients with SLE are at increased risk for the development of atherosclerosis due in large part to poorly-defined lupus-specific risk factors. One such lupus-specific risk factor is thought to be chronic inflammation associated with the autoimmune process. As IRF5 is involved in pro-inflammatory responses we hypothesized that Irf5-deficiency would ameliorate atherosclerosis development in the context of autoimmunity. We therefore examined the role of IRF5 in the gld.apoE-/- mouse model of lupus and lupus-associated atherosclerosis. Irf5-deficiency led to a decrease in splenomegaly, lymphadenopathy, anti-nuclear autoantibody production and the severity of kidney disease. Surprisingly, despite the reduction in systemic autoimmunity, Irf5-deficiency led to a marked increase in the severity of atherosclerosis and to metabolic dysregulation characterized by hyperlipidemia, increased adiposity and insulin-resistance. Bone marrow chimera studies revealed that the pathogenic role of IRF5 in lupus was solely due to its expression in hematopoietic cells. The atheroprotective effect of Irf5 and the suppression of adiposity were found to be due to Irf5 expression in both hematopoietic and non-hematopoietic cells, whereas protection from hyperlipidemia was solely due to the expression of Irf5 in non-hematopoietic cells. Together, our results reveal a role for IRF5 in metabolic homeostasis, as well as in protection against atherosclerosis even in the setting of reduced lupus severity.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第19365号 / 医博第4042号 / 新制||医||1011(附属図書館) / 32379 / 新制||医||1011 / 京都大学大学院医学研究科医学専攻 / (主査)教授 椛島 健治, 教授 佐藤 俊哉, 教授 山田 泰広 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM