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Orientador : Lilian T. Lavras Costallat / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-07-18T20:15:55Z (GMT). No. of bitstreams: 1 Coimbra_IbsenBellini_M.pdf: 1342205 bytes, checksum: a32dca2785723614b083d3a9a6479175 (MD5) Previous issue date: 1993 / Resumo: Tendo em vista os poucos dados referentes às taxas de fertilidade, frequência de abortamentos e sua recorrência entre as mulheres lúpicas em nosso meio, o autor se propõs a estudar a fertilidade numa população de pacientes lúpicas da região de Campinas, comparando-as com uma população de mulheres normais, analisando aocorrência ou recorrência de abortos nestas populações, a frequência dos anticorpos anticardiolipina entre as lúpicas e a importância dos fatores clinicos, laboratoriais e terapêuticos na história gestacional destas pacientes. Foram estudados retrospectivamente 186 pacientes do sexo feminino com Lupus Eritematoso Sistêmico ( LES ) diagnosticados e acompanhados no ambulatório da Disciplina de Reumatologia da Faculdade de Ciências Médicas da UNICAMP. O grupo controle foi constituido por 131 mulheres higidas que compareceram ao pronto socorro do Hospital das Clinicas. A taxa de fertilidade das lúpicas estudadas foi semelhante às da literatura, bem como também à das mulheres normais no Estado de São Paulo. Houve um menor número de gestações entre as pacientes, bem como um maior número de mulheres que nunca engravidaram, quando comparados com as do grupo de mulheres higidas. Houve um número significativamente maior de abortos entre as pacientes, não tendo sido verificada associação com o anticorpo anticardiolipina. Não houve diferenças significativas em relação às manifestações clinicas, laboratoriais e esquemas terapêuticos empregados quando comparadas as lúpicas que engravidaram das que nunca tiveram gestação / Abstract: Although a large proportion of patients with systemic lupus erythemathosus (SLE) are women of reproductive age, aclear picture of the effects of the disease on pregnancy and vice versa was slow to emerge. The initial small retrospective studies of this interaction yielded conflicting results. Confounding factors were the lack of agreed criteria for the diagnosis of exacerbation and the potential confusion among certain features of normal pregnancy and lupus fIare. Besides the lupus effect on fertility rate wasn't ex~lored enough. There are few studies and alI of the~out of our country. In order to study the fertility among SLE patients followed at the State University of Campinas between 1973 to 1992, and to analyse the abortions, anticardiolipin antibody (aCL) freguency and the clinical, laboratorial and therapeutic aspects importa~ce on the reproductive history of those patients,186 lupic patient,s, compared to 131 normal women, were studied retrospectively. The mean age among lupic patients was 32,77 years-old, a~d 33,98 among the controls. The number of pregnancies was lower in patients than in controls, as well as agreater number of patients that never had pregnancy than those ones controlled. Abortions were present in a higher number among the lupic patients and the difference between the groups was Statisticly significant. However, this feature was not related to the aCL positivity. There clinical management had noto were not significant differences and laboratorial features, as well as in the relation to therapeutic among the patients who had pregnancies and those who had not / Mestrado / Mestre em Medicina

Objective: Systemic Lupus Erythematosus (SLE) is a multi‐system disease that predominately affects women. Considering the lack of data on health related quality of life (HRQoL) especially in sub‐ Saharan Africa, we undertook a literature review on HRQoL of SLE patients in developing countries to collate the existing evidence and identify information gaps. A mixed methods qualitative and quantitative study of lived experiences of South African women with SLE was performed. Methods: A literature search was conducted on medical databases using MeSH terms pertaining to HRQoL amongst SLE patients in the developing or low income countries to identify articles published between January 1975 and February 2018. The main study included 25 consenting SLE patients attending two tertiary hospitals in Johannesburg and Cape Town. Individual in‐depth interviews, using a topic guide, were conducted and analysed using NVivo software. In addition, participants completed the Short Form‐36 (SF‐36), Functional Assessment Instrument (FAI) and functional assessment of chronic illness therapy (FACIT) for fatigue questionnaires. The questionnaires were analysed per each tool's scoring method and SPSS software was used to calculate mean, standard deviations and correlations. Results The review of 31 articles, from 11 countries indicated that SLE women have a poor general HRQoL. In addition, we found relationships between disease factors including disease activity, organ damage, functioning, and mental health. Poor socioeconomic status worsened SLE outcomes by limiting patients' access to health care and psychosocial services. In the main study, the majority (72.0%) were black Africans, unemployed (76.0%), with low formal educational level and singlehood status (72.0%). The mean (SD) mental and physical composite SF‐36 scores were poor (50.9 (22.1) and 49.1 (20.5) respectively), and 68.0% of women had FACIT scores of severe fatigue. The mean (SD) FAI was 1.33 (0.8), showing that activities of daily living (ADL) were performed with difficulty. Major themes expressed were fatigue, pain, impaired functioning, depression, pregnancy, aesthetic concerns and sexuality issues. Disease chronicity, fatigue and pain were described by many participants as ‘taking over life' and impacting on performing ADL and career opportunities contributing to indigence. Negative pregnancy outcomes were frequently exacerbated by poor sexual relationships and miscommunication between patient and health care workers. Lack of understanding of SLE by patients, community and family as well as suicidal ideations and depressive symptoms were expressed. Although the quantitative tools measured these aspects, they were unable to explore complexities such as limitations in job acquisition, suicidal ideations, disease understanding and support systems. Conclusion This study underscores the complex, chronic and challenging life experiences, often exacerbated by poverty, of SA women with SLE. Quantitative tools may be inadequate in capturing important aspects of HRQoL that emerged from the qualitive interviews. Awareness of these limitations, together with psycho‐social support and education, might improve HRQoL. This thesis recommends multi‐centred, interventional longitudinal studies that incorporate mixed methods and focus on strategies to improve the negative outcomes in SLE.

Includes bibliographical references / Background: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease commonly affecting females of child-bearing age, hence hormonal changes in pregnancy are thought to play a role in disease activity - often necessitating changes in immunosuppression therapy. SLE is common in Cape Town, however, the effect of pregnancy on SLE and vice versa has not been well characterised. The aim of this study is to report on the pregnancy outcomes of patients with SLE presenting to the maternity department of Groote Schuur Hospital, Cape Town. Methods: This study was designed as a retrospective review of records of pregnant women known with SLE and followed up at the maternity section of Groote Schuur Hospital. The duration of the survey was from 1 January 2003 to 31 December 2013. Records were identified using the attendance registers in the relevant departments. Results: There were 61 pregnancies reviewed in 49 patients; 80.3% of the pregnancies were in patients of mixed ancestry and the rest (19.7%) in black African patients. The mean age at presentation of the current pregnancy was 27215.0 years. Mean gestational age at presentation and delivery was 13.0 ± 6.0 weeks and 28.9 ± 9.8 weeks respectively and 47.5% of the pregnancies were in patients with lupus nephritis (LN). Thirty-nine (63.9%) pregnancies reached the third trimester and 11.5% of all pregnancies ended in the first trimester. There was a lower number of live births to mothers of African ancestry than to those of mixed ancestry (p=0.001). In 55.7% of the pregnancies, no flare was reported while a renal flare was reported in 23%. Pregnancies in patients with LN had higher frequencies of flares (58.6% vs 31.3%; p=D.O32), pre-eclampsia (34.5% vs 12.5%; p=D.O41), longer stay in hospital (12.0 ± 9.1 days vs 6.1 ± 5.1 days; p=0.DO-4) and low birth weight babies (1.94 ± 1.02 kg vs 2.55 ± 0.95 kg; p=D.O46) than in patients without LN. Only 36 (59%) of the neonates were discharged home alive and of these 2 (5.6%) were to mothers of black African ancestry (p=0.001). Conclusion: Increased lupus activity in pregnant SLE patients may account for the increased deaths of neonates born to SLE mothers. Patients of black African descent and those with LN tend to have a poorer outcome. A multi-disciplinary approach to the management of SLE patients (of child-bearing age or pregnant) needs to be further evaluated.

Systemic Lupus Erythematosus (SLE) is an autoimmune disorder associated with the development of immune complexes that deposit in multiple organ systems. The deposition of immune complexes is associated with tissue damage, most commonly seen in the form of kidney damage as lupus nephritis. IRF5 is an SLE susceptibility gene that is causal to type one interferon inflammatory cytokine production. We hypothesized that the peak luminescence of Donkey anti-mouse IgG Alexa-594 and for Goat anti-mouse C3-FITC in FcγRIIB-/- Yaa mice can show the disease state of SLE in murine models at which disease is most active. This thesis demonstrates that peak luminosity in FcγRIIB-/- Yaa mice is at 4.5 months of age. IHC staining was done to show the deposition of IgG and C3 protein in the glomeruli of FcγRIIB-/- Yaa at various ages. It also shows that the disease manifests between the ages of 2-4.5 months of age due to the differences in fluorescence intensity.

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Estrogenic endocrine disrupting chemicals (EEDCs) are defined as chemicals that bind to estrogen receptors (ERs) and augment estrogenic functions, either through promoting or blocking estrogen receptor signaling. Recent reports highlight the growing concern surrounding environmental exposure to EEDCs and immune system modulation. A commonly prescribed EEDC, 17α-ethinyl estradiol, is a synthetic analog of 17β-estradiol (E2), and is also found in many environmental reservoirs of human and animal exposure. Little is known regarding the immunomodulatory effects of this EEDC. Autoimmune diseases, such as systemic lupus erythematosus (SLE), are characterized by a dysregulated immune system that has lost tolerance to self-antigens. The pathogenesis of SLE is still poorly understood. However, it is likely that genetics, epigenetics, hormones, and environmental factors, such as EEDC exposure, contribute to the pathogenesis and severity of SLE. The work presented in this dissertation focused on investigating the immunomodulatory effects of exogenous estrogens in mouse models of SLE. Chapter 1 describes an overview of environmental endocrine disruptors and autoimmune disease, with a particular emphasis on estrogens. Chapter 2 represents a review of the current and pertinent literature surrounding the contributions of sex differences, hormones, and EDCs to the induction of autoantibodies and development of autoimmunity, as well as the contributions of anti- microbial responses to SLE. We explored the contribution of dietary components to SLE disease severity. Mice fed a diet devoid of exogenous phytoestrogens developed significantly reduced glomerulonephritis and glomerular immune complex deposition compared to mice fed a diet containing soy isoflavones. Diet also influenced cytokine production and epigenetics of LPS-stimulated splenic leukocytes. We identified similar effects of E2 and EE implantation with regards to innate immunity, and distinct cellular subset, cytokine production profiles, gene expression, and epigenetic responses between E2 and EE treated NZB/WF1 mice. Oral exposure to a very low human relevant dose of EE promoted glomerulonephritis and augmented responses to viral and bacterial mimics in MRL/lpr mice. Overall, our findings suggest that chronic exposure to environmental EEDCs exacerbates lupus nephritis and alter an already dysregulated immune system in genetically susceptible individuals and have greatly expanded the current body of knowledge surrounding 17α-ethinyl estradiol. / Doctor of Philosophy / Chemicals that can disrupt the normal effects of hormones are termed endocrine disrupting chemicals (EDCs). Estrogenic EDCs promote or suppress the ability of estrogen receptors to carry out normal functions within the body. Normal immune system functions require a fine balance of inflammatory and anti-inflammatory cellular responses. This delicate balance is a prime target for dysregulation by EDC exposure. Autoimmune diseases, such as systemic lupus erythematosus, are characterized by a loss of immune tolerance to ones’ own cells and tissues. There is a lack of knowledge surrounding the immunomodulatory effects of a commonly prescribed EDC, 17α-ethinyl estradiol, especially as it pertains to autoimmune disease patients. The aim of this dissertation work is to investigate the immunomodulatory effects of exogenous EDC exposure in mouse models of SLE. We found that MRL/lpr mice fed a diet devoid of phytoestrogens had reduced kidney disease and immune-complex deposition and had augmented cytokine response and epigenetics in LPS-stimulated splenic leukocytes compared to mice fed a diet high in isoflavones. We next compared the immunomodulatory effects of chronic pharmacologic dose exposure to 17β-estradiol or EE, and found that while both estrogens have similar effects on innate immune cellular responses, EE has distinct effects on T cell population subsets, cytokine production, gene response and epigenetic alterations in female NZB/WF1 mice. Finally, chronic low-dose oral exposure to EE exacerbated clinical signs of kidney disease and suppressed the normal response of toll-like receptor 9 in MRL/lpr mice. Overall, we have found that chronic exposure to environmental estrogenic EDCs exacerbates lupus nephritis and alter an already dysregulated immune system in genetically susceptible individuals.

Chilblain lupus erythematosus is a rare form of cutaneous lupus erythematosus characterized by bluish red infiltrates in acral locations of the body mostly affecting middle-aged women. We recently described a familial form of chilblain lupus manifesting in early childhood caused by a heterozygous mutation in the TREX1 gene, which encodes a 3′-5′ DNA exonuclease. Thus, familial chilblain lupus represents the first monogenic form of cutaneous lupus erythematosus. Here we describe the unusual clinical course of this newly defined genodermatosis in an 18-year-old female member of the family in which familial chilblain lupus was originally described. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Tang, Xiaolin. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 132-144). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.