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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
61

Análise comparativa dos níveis de proteína C-reativa altamente sensível entre indivíduos portadores e não portadores de lesão periapical crônica / Comparative analysis of C-reactive protein in patients with and without chronic apical periodontitis

Brosco, Roberta Esberard 16 September 2009 (has links)
As doenças bucais inflamatórias crônicas, como a doença periodontal, estão relacionadas com a etiopatogênese das doenças arteriais coronarianas, causando danos endoteliais e facilitando a formação das placas ateromatosas. As doenças inflamatórias do periápice, assim como a doença periodontal, são doenças bacterianas que ativam a produção localizada de citocinas e outros mediadores próinflamatórios, como a proteína C-reativa (PCR). Essa proteína tem sido utilizada como um marcador sistêmico da inflamação, infecção e da lesão celular. Suas concentrações podem detectar doenças ocultas no organismo e monitorar a resposta ao tratamento de certos processos inflamatórios e infecciosos. O objetivo desse trabalho foi avaliar se as lesões periapicais crônicas podem ativar a resposta inflamatória, gerando repercussões sistêmicas e determinar se o método da PCR altamente sensível (PCR-as) por imunoturbidimetria pode ser utilizado para o diagnóstico e monitoramento do tratamento endodôntico destas lesões. Assim, comparou-se os níveis plasmáticos da PCR entre 13 indivíduos portadores e 13 indivíduos não portadores de lesão periapical crônica. Foram comparados também os níveis da PCR dos indivíduos portadores de lesão periapical crônica antes e após o tratamento do dente em questão. Não foi possível observar diferenças estatisticamente significantes entre os valores da PCR dos pacientes portadores de lesão periapical crônica antes e após os tratamentos (p=0,9203 com o teste t para amostras emparelhadas e p=0,94427 com o teste Wilcoxon), nem mesmo quando comparou-se os pacientes com lesão periapical crônica com os pacientes controles (p=0,1012 com o teste t para amostras independentes e p=0,1585 com o teste Mann Whitney). Pode-se concluir, com base na metodologia adotada, que as lesões periapicais crônicas não são capazes de induzir uma resposta inflamatória de repercussão sistêmica e o método da PCR-as por imunoturbidimetria não pode ser utilizado para o diagnóstico das lesões periapicais crônicas e nem mesmo para o monitoramento do tratamento endodôntico destas lesões. / Inflammatory effects from periodontal disease can cause oral bacterial byproducts to enter the bloodstream. These effects may cause blood clots that contribute to a coronary heart disease risk factor. Chronic apical periodontitis are also bacterial diseases that stimulate the production of cytokines and other cell-mediated inflammatory factors such as C-reactive protein (CRP). CRP is one of the acute phase proteins that increase during systemic inflammation. Its been suggested that testing CRP levels in the blood may be an additional way to assess cardiovascular disease risk. The aim of this study was to evaluate if chronic apical periodontitis can ativate inflammatory response leading to systemic effects and to determine if a highly sensitive CRP (hs-CRP) assay is available to diagnose and track the endodontic treatment of these lesions. Plasma levels of hs-CRP were compared in blood of 13 individuals with chronic apical periodontitis and 13 healthy controls. CRP levels were also compared in the individuals with chronic apical periodontitis before and after treatment of the tooth. There was no statistical association among CRP levels of individual with or without chronic apical periodontitis (p=0,1012 for t test and p=0,1585 for Mann Whitney test). There was no statistical association among CRP levels of individual with chronic apical periodontitis before and after dental treatments (p=0,9203 for t test and p=0,94427 for Wilcoxon test). In conclusion, these results suggest that chronic apical periodontitis can not ativate inflammatory response leading to systemic effects and even a highly sensitive CRP (hs-CRP) assay is not available to diagnose and track the endodontic treatment of these lesions.
62

Análise comparativa dos níveis de proteína C-reativa altamente sensível entre indivíduos portadores e não portadores de lesão periapical crônica / Comparative analysis of C-reactive protein in patients with and without chronic apical periodontitis

Roberta Esberard Brosco 16 September 2009 (has links)
As doenças bucais inflamatórias crônicas, como a doença periodontal, estão relacionadas com a etiopatogênese das doenças arteriais coronarianas, causando danos endoteliais e facilitando a formação das placas ateromatosas. As doenças inflamatórias do periápice, assim como a doença periodontal, são doenças bacterianas que ativam a produção localizada de citocinas e outros mediadores próinflamatórios, como a proteína C-reativa (PCR). Essa proteína tem sido utilizada como um marcador sistêmico da inflamação, infecção e da lesão celular. Suas concentrações podem detectar doenças ocultas no organismo e monitorar a resposta ao tratamento de certos processos inflamatórios e infecciosos. O objetivo desse trabalho foi avaliar se as lesões periapicais crônicas podem ativar a resposta inflamatória, gerando repercussões sistêmicas e determinar se o método da PCR altamente sensível (PCR-as) por imunoturbidimetria pode ser utilizado para o diagnóstico e monitoramento do tratamento endodôntico destas lesões. Assim, comparou-se os níveis plasmáticos da PCR entre 13 indivíduos portadores e 13 indivíduos não portadores de lesão periapical crônica. Foram comparados também os níveis da PCR dos indivíduos portadores de lesão periapical crônica antes e após o tratamento do dente em questão. Não foi possível observar diferenças estatisticamente significantes entre os valores da PCR dos pacientes portadores de lesão periapical crônica antes e após os tratamentos (p=0,9203 com o teste t para amostras emparelhadas e p=0,94427 com o teste Wilcoxon), nem mesmo quando comparou-se os pacientes com lesão periapical crônica com os pacientes controles (p=0,1012 com o teste t para amostras independentes e p=0,1585 com o teste Mann Whitney). Pode-se concluir, com base na metodologia adotada, que as lesões periapicais crônicas não são capazes de induzir uma resposta inflamatória de repercussão sistêmica e o método da PCR-as por imunoturbidimetria não pode ser utilizado para o diagnóstico das lesões periapicais crônicas e nem mesmo para o monitoramento do tratamento endodôntico destas lesões. / Inflammatory effects from periodontal disease can cause oral bacterial byproducts to enter the bloodstream. These effects may cause blood clots that contribute to a coronary heart disease risk factor. Chronic apical periodontitis are also bacterial diseases that stimulate the production of cytokines and other cell-mediated inflammatory factors such as C-reactive protein (CRP). CRP is one of the acute phase proteins that increase during systemic inflammation. Its been suggested that testing CRP levels in the blood may be an additional way to assess cardiovascular disease risk. The aim of this study was to evaluate if chronic apical periodontitis can ativate inflammatory response leading to systemic effects and to determine if a highly sensitive CRP (hs-CRP) assay is available to diagnose and track the endodontic treatment of these lesions. Plasma levels of hs-CRP were compared in blood of 13 individuals with chronic apical periodontitis and 13 healthy controls. CRP levels were also compared in the individuals with chronic apical periodontitis before and after treatment of the tooth. There was no statistical association among CRP levels of individual with or without chronic apical periodontitis (p=0,1012 for t test and p=0,1585 for Mann Whitney test). There was no statistical association among CRP levels of individual with chronic apical periodontitis before and after dental treatments (p=0,9203 for t test and p=0,94427 for Wilcoxon test). In conclusion, these results suggest that chronic apical periodontitis can not ativate inflammatory response leading to systemic effects and even a highly sensitive CRP (hs-CRP) assay is not available to diagnose and track the endodontic treatment of these lesions.
63

Avaliação da Proteína C Reativa como marcador inflamatório e de seu potencial para monitoração terapêutica em casos de pênfigo foliáceo e de piodermite superficial na espécie canina / Evaluation of C- Reactive Protein as an inflammatory marker and its potential for therapeutic monitoring in cases of canine pemphigus foliaceus and superficial pyoderma in dogs

Júlia Só Severo 19 August 2015 (has links)
O pênfigo foliáceo inclui-se em um grupo de dermatoses autoimunes vésico-bolhosas da pele e mucosas reconhecido em alguns mamíferos, incluíndo os cães. Muitos autores acreditam que o pênfigo foliáceo (PF) é a dermatopatia autoimune mais frequentemente observada em caninos. Muitas podem ser as enfermidades caninas que devem ser incluídas no diagnóstico diferencial do pênfigo foliáceo, principalmente, a piodermite superficial (PS). A Proteína C Reativa (PCr) é conhecida como a principal proteína de fase aguda em cães. Nesses espécimes, a elevação da PCr tem sido observada em ampla variedade de condições mórbidas. A determinação da PCr tem sido proposta como um marcador inflamatório de algumas doenças autoimunes. O objetivo deste estudo foi determinar se a Proteína C Reativa pode ser utilizada como um marcador biológico precoce para diferenciar o pênfigo foliáceo da piodermite superficial em cães. Esta pesquisa constituiu um estudo clínico observacional prospectivo longitudinal, realizada em cães acometidos pelo PF ou PS. Foram incluídos 59 cães divididos em três Grupos I (Controle) com 31 animais, II (PF) e III (PS), cada um constituído por 14 cães. Submeteram-se, respectivamente, fragmentos cutâneos e soros de caninos, acometidos por PF ou PS, a exames histopatologicos e imunofluorescência direta (IFD) e à determinação de PCr e, também, a imunofluorescência indireta (IFI), utilizando-se para essa última coxins palmo-plantares a título de substrato. O grau de acometimento dos pacientes penfigosos (Grupo II) foi avaliado pelo PEFESI, durante período de até 90 dias, em diferentes momentos em que se realizou a IFI e a avaliação da PCr. Comparando-se os valores de IFD com aqueles da histopatologia obtiveram-se valores geral de concordância de 75% (9/12) e Índice Kappa de 0,77 (p<0,001) e, também, concordância dita substancial entre os dois métodos. Já, na IFI o valor de concordância foi de 100% (14/14), o de Kappa de 1,0 (p<0,001), com concordância considerada perfeita entre a IFI e a histopatologia. O Grupo II apresentou maior valor de mediana de PCr (37,4&micro;g/mL) quando comparado aos Grupos I, com 2,9 &micro;g/mL (p<0,0001) e III, com 3,8 &micro;g/mL (p=0,008). Não houve diferença entre os Grupos I e III (p=0,178). Considerando-se como ponto de corte um valor de PCr > 10,6&micro;g/mL, a chance de um animal estar acometido pelo PF é 5,5 vezes maior àquela de um cão não afetado, o que equivale a uma probabilidade pós-teste de 84,6%, conferindo um acréscimo de 34,6% na capacidade de diagnóstico do PF. Conclui-se que determinação de PCr é de inequívoca valia para o estabelecimento de diferenciação diagnóstica entre a casuística da contumaz piodermite superficial com quadros do pênfigo foliáceo canino / Pemphigus is included in a group of skin and mucous autoimmune vesicobullous dermatoses recognized in some mammals, including dogs. Many authors believe that pemphigus foliaceus (PF) is the autoimmune skin disease most often observed in dogs. Many must be the canine diseases considered in the pemphigus foliaceus differential diagnosis, especially the superficial pyoderma (SP). The C-Reactive Protein (CRP) is known as a major acute phase protein in dogs. The CRP increase has been observed in a wide variety of morbid conditions in dogs. The determination of CRP has been proposed as an inflammatory marker of some autoimmune diseases. This study aimed to determine whether C-Reactive Protein can be used as an early biomarker to differentiate pemphigus foliaceus of superficial pyoderma in dogs. An observational prospective longitudinal clinical study was undertaken including dogs affected by PF or PS. Fifth nine dogs were divided into three groups: Group I (Control) with 31 animals and II (PF) and III (SP), consisting of 14 dogs each. Dogs affected by PF or SP had skin fragments submitted to histopathological examination and direct immunofluorescent reaction (DIF). The blood sera were used to determine the CRP concentration, and also to perform the indirect imunofluorescent reaction (IIF) using canine footpad as substrate. The pemphigus patients (Group II) clinical involvement degree was evaluated by PEFESI, over a period of 90 days, moments in which IFI and evaluation of CRP took place. Comparing the DIF values with the histopathology there was an agreement of 75% (9/12) with a Kappa index of 0.77 (p <0.001) which means a degree of substantial arrangement between the two methods. Considering IIF, the agreement value was 100% (14/14) with Kappa index of 1.0 (p<0.001), showing perfect arrangement between the IIF and the histopathology. Group II showed higher CRP median (37.4 mg / mL) compared to Groups I, with 2.9 mg / mL (p <0.0001) and III with 3.8 mg / mL (p = 0.008 ). There was no statistic difference between groups I and III (p = 0.178). Considering CRP> 10,6&micro;g / mL as a cutoff value, the chance of an animal having PF is 5.5 times higher than not to be, which is equivalent to a post-test probability of 84,6%, giving a 34.6% increase in the PF diagnostic capability. It concludes that determination of CRP is unequivocal asset for the establishment of diagnostic differentiation between the common superficial pyoderma to canine pemphigus foliaceus
64

Avaliação e comparação da dor e da resposta inflamatória pós-cirúrgica em cadelas submetidas à ovário-histerectomia laparoscópica com único portal; realizada com pinça bipolar com corte e coagulação simultâneos ou por miniceliotomia com ganho de Snook /

Coutinho, Alexandre José. January 2013 (has links)
Orientador: Gilson Hélio Toniollo / Banca: Maricy Apparício Ferreita / Banca: Nereu Carlos Prestes / Resumo: Os procedimentos cirúrgicos contraceptivos possuem como finalidades promover o controle populacional de animais de companhia e evitar ou tratar enfermidades do trato reprodutor. No entanto, são traumáticos e implicam em dor pós-operatória, assim como outras complicações. Portanto faz-se necessário o estudo de técnicas minimamente invasivas que oferecem benefícios, como menor trauma tissular, menor risco de contaminação e recuperação mais rápida. O presente estudo teve como objetivo comparar tempo cirúrgico, complicações intraoperatórias, dor, níveis de glicemia e resposta inflamatória medida pela proteina C reativa, pós-operatória em cadelas submetidas à ovario-histerectomia laparoscópica por único portal, usando pinça bipolar com corte e coagulação simultâneos para a hemostasia e secção dos pedículos ovarianos ou por miniceliotomia com gancho de Snook. Para esses procedimentos foram utilizadas vinte e quatro cadelas hígidas, divididas em dois grupos de igual número. Entre os dois grupos apenas a glicemia foi significantemente maior na técnica de minilaparotomia do que no grupo vídeocirugia. As demais avaliações não tiveram diferença significativa entre os grupos avaliados / Abstract: Surgical procedures have contraceptive purposes as promoting population control of pets and prevent or treat diseases of there productive tract. However, they are traumatic and involve post operative pain, as well as other complications, so it is necessary to study minimally invasive techniques that offer benefits such as less tissue trauma, less risk of infection and faster recovery. The present study aimed to compare operative time, intra operative complications, pain, blood glucose and inflammatory response as measured by C-reactive protein, post operative in bitches undergoing laparoscopic ovarian-hysterectomy for only portal, using bipolar forceps with cut and for simultaneous coagulation for hemostasis and section of the ovarian pedicles or by mini laparotomy with a hook Snook. For to these procedures were used twenty-four healthy dogs, divided into two equal groups. Between the two groups only glucose was significantly higher in the case mini laparotomy than in the video cirugic group. Other evaluations showed no significant difference between the groups / Mestre
65

Marital Quality and Cardiovascular Risk in Women During the Menopausal Transition

Brown, Tracy E. 01 July 2017 (has links)
Marital quality is linked to health benefits for men and women. Although women have less risk factors than men for cardiovascular disease prior to menopause, their risk increases substantially after menopause. The purpose of this study was to assess the impact of marital quality and vasomotor symptoms on cardiovascular risk factors including C-reactive protein (CRP) and carotid intima-media thickness (cIMT) in women before, during, and after the menopausal transition. The final sample consisted of 92 married women between the ages of 40 and 60 years. Hypotheses were tested using hierarchical regression and general linear modeling. Results suggest that greater marital quality reduces the negative effect of a lower level of vasomotor symptoms on cIMT but not CRP. Contrary to hypotheses, marital quality did not predict CRP or cIMT and vasomotor symptoms were not correlated with CRP or cIMT. While analyses did not support an interaction between menopausal status and lower marital quality on vasomotor symptoms or CRP, there was limited support for an interaction between menopausal status and lower marital quality on cIMT (p = .057) suggesting that for postmenopausal women higher marital quality is related to lower levels of cIMT. Overall, findings suggest that it is important to consider the impact of psychosocial aspects of a middle aged woman's life (i.e., marital quality) in conjunction with biological stressors when assessing cardiovascular risks in women during the menopausal transition.
66

The Inflammatory Consequences of Stress and Adiposity

Bykowski, Cathy A 13 February 2008 (has links)
The inflammatory process is important in protecting the body against the invasion of pathogens, but recent research has suggested that a long-term inflammatory response may lead to chronic diseases (e.g., Black, 2003; Wu, Dorn, Donahue, Sempos, & Trevisan, 2002). Two factors that have been implicated in the inflammatory and disease processes are stress and obesity (Black, 2003). While their individual lines of research continue to grow, few researchers have attempted to integrate these factors into one model to explain their effects on inflammation. This study aimed to replicate previous findings suggesting relationships between stress, obesity and inflammation and test an integrated model of stress and obesity by examining a possible interaction between the effects of stress and obesity on inflammation. Socioeconomic Status (SES) and depression were employed to examine the association between stress and the inflammatory marker, c-reactive protein (CRP). The study utilized the data resulting from the National Health and Nutrition Examination Survey (NHANES; National Center for Health Statistics, 2006). Included in the dataset are 4998 adults (2416 males and 2582 females) ranging in age from 18 years to over 85 years (M = 47.13, SD = 20.86). A subsample (N = 589) completed the Major Depression module of the Composite International Diagnostic Interview (CDCI). The results indicate that body mass index, waist circumference, income, education, and depression symptoms significantly predict CRP. The data also suggest an interaction between the adiposity variables and the SES variables. This supports the hypothesis that the inflammatory effect of stress on an individual is moderated by adiposity.
67

Body composition, physical activity and C-reactive protein in children : the PLAY study / B. Harmse

Harmse, Berna January 2006 (has links)
Thesis (M.Sc. (Nutrition))--North-West University, Potchefstroom Campus, 2007.
68

A matched case control study of the nutritional status of newly diagnosed tuberculosis patients and tuberculosis free contacts in Delft, Western Cape

Lombardo, Candice Clarissa January 2011 (has links)
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mso-ascii-font-family:Calibri / mso-ascii-theme-font:minor-latin / mso-hansi-font-family:Calibri / mso-hansi-theme-font:minor-latin / mso-bidi-font-family:"Times New Roman" / mso-bidi-theme-font:minor-bidi / mso-ansi-language:EN-US / mso-fareast-language:EN-US / } </style> <![endif]--><b style="mso-bidi-font-weight: normal"><span lang="EN-GB">Background</span></b><span lang="EN-GB">: Malnutrition is a risk factor for the development of pulmonary tuberculosis (TB) and may be responsible for the premature deaths of patients with active disease. An adequate nutritional status may therefore be protective in delaying the onset from latent infection to active disease. In South Africa, very little data is available on the nutritional status of adults who present with tuberculosis. This study therefore aims to compare the nutritional status of newly diagnosed pulmonary tuberculosis patients with TB-free controls.</span> <b style="mso-bidi-font-weight: normal"><span lang="EN-GB">Study population &amp / Design</span></b><span lang="EN-GB">: This is a community based case-control study. Forty-three newly diagnosed pulmonary tuberculosis patients were recruited as cases and matched according to age, gender and race to 43 TB-free close contacts. HIV positive subjects were excluded from the study.</span> <b style="mso-bidi-font-weight: normal"><span lang="EN-GB">Methods</span></b><span lang="EN-GB">: Each participant was interviewed and completed a structured questionnaire to obtain demographic information. Weight was measured to the nearest 0.1kg and height to the nearest 1mm. A 24-hr dietary recall method was used to obtain dietary information. Biochemical analysis was carried out to measure&nbsp / concentrations of transferrin, albumin, CRP, ferritin, zinc, copper, vitamin A and E.</span> <b style="mso-bidi-font-weight: normal"><span lang="EN-GB">Results</span></b><span lang="EN-GB">: The median Body Mass Index (BMI) for cases was 18.80kg/m&sup2 / (IQR 14.35, 32.11) and TB-free contacts 21.17 kg/m&sup2 / (IQR 16.75, 34.98) with a significant difference between the groups of p=0.001. There was significant difference in weight (p=0.002) and MUAC (p=0.000) between groups. No significant difference in dietary intake of energy (KJ) (p=0.695), protein (p=0.804), CHO (p=0.801) and fat ( p=0.796) was found between groups. There was a statistically significant increase in ferritin (p=0.000) and C-reactive protein (CRP) (p=0.000) in TB patients, while albumin (p=0.000), serum zinc (p=0.000) and serum vitamin A (p=0.000) were statistically significantly lower among cases.</span> <b style="mso-bidi-font-weight:normal"><span lang="EN-GB">Conclusion</span></b><span lang="EN-GB">: There was no significant difference in the macronutrient intake of TB cases and TB-free contacts, although a significant difference was seen in BMI, MUAC and weight between groups, with all these parameters being lower in TB patients. Ferritin and CRP levels were markedly increased in TB cases while serum zinc, vitamin A and albumin are all significantly lower in&nbsp / TB patients than TB free contacts.</span> <b style="mso-bidi-font-weight:normal"><span lang="EN-GB">&nbsp / </span></b></p> <p>&nbsp / </p>
69

Serum High Sensitivity C-Reactive Protein, White Blood Cell Count, and High-Density Lipoprotein Cholesterol Levels are Associated with Coronary Artery Lesions in Kawasaki Disease

Ou, Chum-yen 04 July 2007 (has links)
Background: Kawasaki disease (KD) affects mainly children younger than five years of age, leading to coronary artery lesions, and even to life-threatening myocardial infarctions. Since 1976, Kawasaki disease has occurred among thousands of children in Taiwan. Evidence suggests that inflammation plays a key role in the pathogenesis of atherosclerosis. Significant determinants of high sensitivity C-reactive protein (hs-CRP), which is a sensitive indicator of inflammation, as well as white blood cell (WBC) count, and high-density lipoprotein cholesterol (HDLc) and coronary artery lesion were identified. The relationships between these factors¡¦ concentration and arterial lesion were likewise investigated and had reported. The aim of this study was to determine the serum levels of the hs-CRP, WBC count, and plasma HDLc levels in patients with later phase of KD. Methods and Materials: From July 2005 to June 2006, 97 children with Kawasaki disease at least 1 year after diagnosis were recruited in this study. These participated children had been diagnosed as KD and collected at the interval of 2001 to 2004. Diagnosis was based on the 1984 revised by the KD Research Committee in Japan. The participants were grouped into 45 patients with KD and coronary aneurysms (Group I), 52 patients with KD and normal coronary arteries (Group II), and 50 healthy age-matched children (Control Group III). Their WBC count, systemic and diastolic blood pressures, body mass index, age, sex, fasting total cholesterol concentrations, triglyceride, high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol, serum hs-CRP levels, and coronary artery lesion by cardioechography were recorded and compared. The analytical differences between hs-CRP, WBC count, and plasma HDLc levels and the coronary artery events in KD were examined. Results: Serum hs-CRP levels of Group I patients (mean 0.264 mg/dl) was significantly greater than that of Group II (mean 0.155 mg/dl, p=0.006) and Group III patients (mean 0.116 mg/dl, p =0.017). Similarly, the WBC count of Group I patients (mean 6,543.11/mm3) was significantly greater than that of Group II (mean 5,720.19/mm3, p=0.029), and Group III patients (mean 5,611.27/mm3, p =0.012). However, plasma HDLc levels of Group I patients (mean 41.42 mg/dl) was significantly lesser than that of Group II (mean 44.79 mg/dl, p=0.035), and Control Group III patients (mean 46.58 mg/dl, p=0.027). There was a positive association between hs-CRP and WBC count levels (r = 0.641, p < 0.05), but none between hs-CRP and plasma HDLc levels. Conclusions: There is the possibility of ongoing low-grade inflammation late after the convalescent phase of Kawasaki disease in children with coronary aneurysms, which may have a role in increasing coronary artery dysfunction. These results also suggest that hs-CRP, WBC count, and plasma HDLc levels are useful parameters for predicting formation of coronary artery lesion even in children after onset of KD.
70

C-reactive protein (CRP) and anti-CRP autoantibodies in systemic lupus erythematosus : a study on the occurrence and clinical implications of anti-CRP antibodies and CRP-mediated complement activation

Sjöwall, Christopher January 2006 (has links)
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by production of a wide range of autoantibodies, multiple organ involvement and by local formation or tissue deposition of immune complexes (ICs) in the inflamed organs. In contrast to most systemic inflammatory conditions, and despite raised levels of pro-inflammatory cytokines, SLE flares are rarely reflected by elevated C-reactive protein (CRP), an important acute-phase reactant in man with homologs in vertebrates and several invertebrates. As a part of the innate immune system, CRP binds certain molecules exposed on the surface of dying cells/apoptotic bodies and on the surface of pathogens and mediates their elimination by uptake in the reticuloendothelial system. CRP also interacts with IgG-containing immune complexes, binds Fc receptors and activates the complement system via C1q. The aims of this thesis were to investigate the complement activation properties of CRP; to elucidate if anti-CRP antibodies occur in SLE and, if so, whether anti-CRP antibody levels correlate with disease activity in SLE; to test the hypothesis that autoantibodies to pro-inflammatory cytokines prevent rise of CRP; and to survey if autoantibodies to certain nuclear antigens or to CRP correlate with cytokine-inducing properties of ICs from SLE sera. We have demonstrated that CRP bound to phosphorylcholine is a powerful activator of the classical complement pathway already in the CRP concentration range 4 to 10 mg/L, but with a marked inhibition at CRP levels above 150 mg/L. Autoantibodies to the monomeric form of CRP were found in approximately 40 percent of SLE patients and in a few sera from patients with primary Sjögren’s syndrome, but not in rheumatoid arthritis or in inflammatory bowel disease. The anti-CRP antibody levels showed significant correlations to several laboratory and clinical measurements, and anti-CRP positivity was associated with renal involvement in SLE. Native CRP levels were not correlated with anti-CRP or anti-cytokine antibody levels. Hence, the presence of antibodies to monomeric CRP or to CRP-inducing cytokines is an unlikely explanation to the relative failure of CRP response in patients with active lupus. However, antibodies to TNFα were found in subnormal levels at disease flares, whereas antibodies to TGFβ were found in supranormal levels as compared to healthy subjects. In contrast to antibodies against CRP and DNA, anti-SSA and anti-SSB antibodies may regulate the inflammatory process in SLE by enhancing IC formation and subsequent production of cytokines such as IL-6, IL-10 and IL-12p40. Hypothetically, anti-CRP autoantibodies may be of pathogenic importance, for instance by binding to monomeric CRP on cell and tissue surfaces and thereby increasing the risk of extrahepatic deposition of apoptotic material and in situ formation of ICs. / On the day of the defence data the status of article I was Submitted and the tile was "C-reactive protein activates or inhibits the classical complement pathway in a concentration dependent manner" and the status of article V was: Submitted.

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