Darbo tikslas: nustatyti reumatoidinio artrito (RA), seronegatyvių spondiloartropatijų (SpA) bei sisteminės raudonosios vilkligės (SRV) paplitimą Vilniaus mieste. Darbo metodika: Buvo atlikti 3 tyrimai: 1. RA ir SRV paplitimo Vilniaus mieste apskaičiavimas, remiantis Vilniaus miesto RA ir SRV sergančių asmenų duomenų baze; 2. RA ir SRV paplitimo Vilniaus mieste populiacinis tyrimas, apklausiant Vilniaus miesto gyventojus paštu; 3. RA ir SpA paplitimo Vilniaus mieste populiacinis tyrimas, apklausiant Vilniaus miesto gyventojus telefonu. Rezultatai: remiantis Vilniaus miesto RA ir SRV sergančiųjų duomenų baze, RA paplitimas Vilniaus mieste 2004m. pabaigoje buvo 0,14% (95% PI 0,13-0,15). Apskaičiuotas SRV paplitimas Vilniuje 2004m. pabaigoje buvo 0,0174% arba 17,4/100 000 gyventojų (95% PI 0,0137-0,0218). Atlikus RA ir SRV paplitimo tyrimą (apklausą paštu), nustatyta, kad RA paplitimas Vilniuje yra 0,37% (95% PI 0,21-0,62), o SRV paplitimas – 0,0498% (95% PI 0,006-0,180). RA paplitimas buvo standartizuotas pagal amžių ir lytį, remiantis 2004m. pradžios Vilniaus miesto populiacija, apskaičiuotas standartizuotas RA paplitimas yra 0,32% (95% PI 0,18-0,57). Atlikus RA ir SpA paplitimo tyrimą (apklausą telefonu), apskaičiuotas RA paplitimas buvo 0,76% (95% PI 0,44-1,24), o SpA paplitimas - 0,62% (95% PI 0,33-1,06). RA ir SpA paplitimas buvo standartizuotas pagal amžių ir lytį, remiantis 2004m. pradžios Lietuvos populiacija, apskaičiuotas standartizuotas RA paplitimas yra 0,51% (95%... [toliau žr. visą tekstą] / Objective: to assess the prevalence of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and spondyloarthropathy (SpA) in Vilnius, Lithuania. Methods: 3 prevalence studies were conducted: 1. Registry-based study of the prevalence of RA and SLE; 2. Population-based study of the prevalence of RA and SLE (interview conducted by mail); 3. Poulation-based study of the prevalence of RA and SpA (interview conducted by telephone). Results: according to the Vilnius RA and SLE registry, the prevalence of RA in Vilnius at the end of year 2004 was 0,14% (95% CI 0,13-0,15), and the prevalence of SLE was 0,0174% or 17,4/100 000 (95% CI 0,0137-0,0218). The population-based study, conducted by mail, revealed 15 RA and 2 SLE cases, accounting for a prevalence rate of RA of 0,37% (95% CI 0,21-0,62), and a prevalence of SLE rate of 0,0498% (95% CI 0,006-0,180). The standardized prevalence rate according to age and sex in the Vilnius population showed an RA prevalence of 0,32% (95% CI 0,18-0,57). The population-based study, conducted be telephone, detected 16 RA and 13 SpA cases, resulting in a crude prevalence of 0,76% (95% CI 0,44-1,24) for RA and 0,62% (95% CI 0,33-1,06) for SpA. The standardized prevalence rate according to age and sex in the Vilnius population showed an RA prevalence of 0,51% (95% CI 0,29-0,96) and a SpA prevalence of – 0,75% (95% CI 0,38-1,40).

Autoimmune diseases are clinical manifestations of a loss-of-tolerance of the immune system against the body’s own substances and healthy tissues. Primary Sjögren’s syndrome (pSS) and systemic lupus erythematosus (SLE) are two chronic inflammatory autoimmune diseases characterized by autoantibody production and an activated type I interferon system. Although the precise mechanisms leading to autoimmune processes are not well defined, recent studies suggest that aberrant DNA methylation and gene expression patterns may play a central role in the pathogenesis of these disorders. The aim of this thesis was to investigate DNA methylation and gene expression in pSS and SLE on a genome-wide scale to advance our understanding of how these factors contribute to the diseases and to identify potential biomarkers and novel treatment targets. In study I, differential DNA methylation was analyzed in multiple tissues from pSS patients and healthy controls. We identified thousands of CpG sites with perturbed methylation; the most prominent finding was a profound hypomethylation at regulatory regions of type I interferon induced genes in pSS. In study II, a cases-case study comparing DNA methylation in pSS patients with high fatigue to patients with low fatigue, we found methylation patterns associated to the degree of fatigue. In study III, RNA-sequencing was applied to investigate the transcriptome of B cells in pSS in comparison to controls. Increased expression of type I and type II interferon regulated genes in pSS was observed, indicating ongoing immune activation in B cells. In study IV, the impact of DNA methylation on disease susceptibility and phenotypic variability in SLE was investigated. We identified DNA methylation patterns associated to disease susceptibility, SLE manifestations and different treatments. In addition, we mapped methylation quantitative trait loci and observed evidence for genetic regulation of DNA methylation in SLE.   In conclusion, the results presented in this thesis provide new insights into the molecular mechanisms underlying autoimmunity in pSS and SLE. The studies confirm the central role of the interferon system in pSS and SLE and further suggest novel genes and mechanisms to be involved in the pathogenesis these autoimmune diseases.

Introduktion: Systemisk Lupus Erythematosus är en prototypisk autoimmun sjukdom som gör att immunförsvarets antikroppar angriper kroppens egna vävnader, vilket leder till kronisk inflammation i kroppens organsystem. Idag finns ingen verksam behandling för Systemisk Lupus Erythematosus. Syftet med denna studie var att undersöka hur Dvitamintillskott påverkar Systemisk Lupus Erythematosus. Metod: Artiklarna hittades i databasen ”Pubmed” med sökningen ”Systemic Lupus Erythematosus and vitamin D supplementation”. Bland sökresultaten fanns sex relevanta artiklar som hade undersökt effekten av D-vitamintillskott på SLE. Resultat: Mer än hälften av patienterna i samtliga studier nådde serum 25(OH) D-nivåer som ansågs vara tillräckliga. D-vitamintillskottet minskade Th1/Th17-cellerna men ökade också Treg-celler och Th2-celler. Tre studier visade sig ha en signifikant minskning i sjukdomsaktivitet och anti-dsDNA antikroppar. Komplement C3 minskade i studie 2. Diskussion: Fem av studierna tyder på att oral administrering av D-vitamin tillskott har gett positiv inverkan på SLE. Två av de granskade studierna rapporterades inge positiv klinisk effekt hos deltagarna. Slutsats: D-vitamintillskott dämpar immunsystemet genom att öka Treg-celler och Th-2-celler men även minska Th1/Th17-celler och B-celler samt produktionen av autoantikroppar och anti-dsDNA-antikroppar. Effekten av D-vitamintillskott på komplement C3 och C4 är oklar. Det krävs dock fler studier med fler deltagarantal för att dra en slutsats om Dvitamintillskott kan användas som behandling för SLE. / Background: Systemic Lupus Erythematosus is a prototypical autoimmune disease in which antibodies attack healthy tissues in the body, causing inflammation in several organs. Aim: The aim of this literature study was to investigate the effect of Vitamin Dsupplementation on SLE. Method: The articles were searched in the database called ”Pubmed” using the search terms ”Systemic Lupus Erythematosus and Vitamin D supplementation”. Six of the articles which examined the effects of D-vitamin supplementation on SLE were relevant for this study. Result: More than half of the patients in all six studies reached sufficient serum 25(OH)D. Vitamin D-supplement reduced Th1/Th17-cells but increased Tregs-cells and Th2-cells. 3 studies showed a decrease in disease-activity and anti-dsDNA. C3 decreased in study 2. Discussion: Five studies indicated that the oral administration of vitamin-D supplementation had a positive effect on SLE. Two of the examined studies did not observe any clinical effect of the vitamin-D supplement. Conclusion: Vitamin-D supplement suppresses the immunesystem by increasing Treg cells and Th-2 cells but also reducing Th1/Th17-cells and B-cells as well as the production of autoantibodies and anti-dsDNA antibodies. The effect of vitamin D-supplement is unclear. More studies with more participants are required to determine if vitamin-D supplement can be used as a treatment for SLE.

OBJETIVO. Identificar fatores preditivos para o desenvolvimento da osteonecrose (ONA) em pacientes com Lúpus Eritematoso Sistêmico (LES) de diagnóstico recente. METODOLOGIA. Quarenta e seis pacientes consecutivos, de uma coorte informatizada no ambulatório de LES do serviço de Reumatologia do Hospital das Clínicas de São Paulo, participaram deste protocolo que ocorreu entre julho de 2004 e julho de 2005. Os critérios de inclusão foram: pacientes do sexo feminino; menos de cinco anos de diagnóstico de LES; e idade maior que 18 anos. Todas as pacientes foram submetidas à ressonância nuclear magnética (RNM) dos quadris para o diagnóstico de ONA, independente da sintomatologia. Variáveis clínicas foram obtidas através de prontuários médicos, entrevista e exame clínico. Variáveis laboratoriais incluíram: lipoproteínas séricas, auto-anticorpos, fatores trombofílicos e de hipofibrinólise. Densidade mineral óssea foi medida através da densitometria de dupla emissão de raios-X. Fraturas vertebrais foram investigadas através da realização de radiografias da coluna. RESULTADOS. A ONA foi encontrada em 10 das 46 pacientes. Idade, duração de doença e raça não diferiram entre pacientes lúpicas com e sem ONA. Comparações envolvendo as várias manifestações clínicas do LES, perfil lipoprotéico e de auto-anticorpos, freqüência de trombofilia e hipofibrinólise também não foram estatisticamente diferentes entre os grupos. A freqüência de pacientes com SLEDAI ?8 no ano anterior ao diagnóstico clínico de ONA foi significativamente maior (60%) do que no grupo sem ONA considerando-se o ano anterior à entrada no estudo (19,4%), p=0,011. Corroborando com esse achado, a dose cumulativa de glicocorticóide (GC) utilizada no anterior ao diagnóstico de ONA foi maior quando comparada ao ano anterior à entrada no estudo(p=0,045). Não foram observadas diferenças com relação aos dados densitométricos e radiográficos da coluna. Na análise multivariada somente o SLEDAI permaneceu como fator de risco independente para ONA (OR=6,6, IC=1,07-41,29, p=0,042). CONCLUSÃO. Este estudo revela que a atividade de doença no ano anterior ao diagnóstico clínico de ONA é fator de risco preponderante para o desenvolvimento desta complicação no LES recente. / OBJECTIVE. To evaluate predictive factors for osteonecrosis (ON) development in patients with early Systemic Lupus Erythematosus (SLE). METHODS. Forty-six consecutive SLE patients from an electronic cohort in a Lupus Clinic from the Rheumatology Division in the University of São Paulo were enrolled on this study that occurred between July 2004 and July 2005. Inclusion criteria were female gender, age > 18 years-old and less than 5 years of disease duration. All patients underwent magnetic resonance imaging (MRI) of the hips for ON diagnosis irrespective of symptoms. Clinical variables were obtained through medical records, interview and physical examination. Laboratory variables were: serum lipoproteins, autoantibodies profile, trombophilia and hypofibrinolysis factors. Bone mineral density was acquired through dual energy x-ray absorptiometry. Vertebral fractures were investigated by spine X-rays. RESULTS. ON was found in 10 of 46 patients. Age, disease duration and race did not differ between patients with and without ON. The frequency of clinical features, lipoprotein and auto-antibodies profile and frequency of trombophilia and hypofibrinolysis were also alike in the two groups. Importantly, disease activity (frequency of patients with SLEDAI ?8) in the previous year of ON clinical diagnosis was significantly higher when compared to patients without ON in the previous year of study entrance (60.0% vs. 19.4%, p=0.011). Reinforcing this finding, glucocorticoid cumulative dose used in the previous year of ON diagnosis was also higher compared to SLE without ON in the previous year of study entrance (p=0.045). Differences concerning the densitometric and radiographic data were not observed. Remarkably, in the multivariate analysis only SLEDAI remained as an independent risk factor for ON (OR=6.6, CI=1.07-41.29, p= 0.042). CONCLUSION. This study has clearly revealed that disease activity in the previous year of ON clinical diagnosis is the main predictor factor for the development of this complication in early SLE.

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: 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

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 caracterizada por hiperatividade imunológica crônica pela ação de autoanticorpos que afetam diversos órgãos. Embora o uso crônico de imunossupressores predisponha o paciente a infecções, poucas pesquisas avaliaram uma possível associação entre doença periodontal e LES. Os objetivos deste trabalho foram investigar, por meio de estudo caso-controle, a prevalência e a gravidade da doença periodontal em pacientes com LES, e identificar e quantificar as principais bactérias periodontais presentes no biofilme subgengival. Foram incluídas 60 mulheres em atendimento no Setor de Reumatologia do Hospital Universitário de Brasília, de 20 a 65 anos de idade, sendo subdivididas em LES-A (ativo; n= 31) e LES-I (inativo; n=29). O grupo controle foi composto por 31 mulheres com os mesmos critérios de inclusão, porém sem doenças sistêmicas. As pacientes foram avaliadas quanto às medidas de profundidade de sondagem (P.S), perda de inserção clínica (PIC), índice de sangramento do sulco (ISS) e índice de placa (IPl) no exame inicial. Foram coletados biofilmes subgengivais dos quatro sítios mais profundos para identificação e quantificação de periodontopatógenos por meio de hibridação DNA-DNA checkerboard. Não houve diferenças estatisticamente entre os grupos relativamente aos parâmetros clínicos periodontais, exceto para o ISS, que foi menor no LESA (11,19% ± 14,62%) comparativamente ao grupo controle (17,30% ± 14,88%), porém sem diferenças quando comparado com o grupo LES-I (11,34% ± 11,59%). Houve baixa prevalência de bolsas periodontais, de PIC 4 mm e de espécies de Actinomyces em todos os grupos. Verificou-se aumento na contagem de bactérias do complexo vermelho no grupo LES-I (4,07 x 105; 95% CI: 0,16-0,79) em relação ao grupo controle (2,50 x 105; 95% CI: 1,23-3,77), com diferenças estatisticamente significante apenas referente ao grupo LES-A (p< 0,05; Kruskal Wallis pós-teste Dunn; 0,45 x 105; 95% CI: 0,16-0,79). Os resultados desse estudo demonstraram que os parâmetros periodontais são semelhantes entre pacientes com LES e grupo controle. O grupo de LES-I apresentou maior tempo dessa doença; aumento da contagem de microorganismos (especialmente dos complexos vermelho e verde em amostras de biofilme subgengival) e pior condição periodontal. / Systemic lupus erythematous (SLE) is an autoimmune disorder characterized by chronic immunological hyperactivity resultant from the action of autoantibodies, affecting many organs. Although the use of immune suppressors may predispose infections, few studies have investigated the prevalence and severity of periodontal disease in SLE patients. The aim of this study is to investigate the prevalence and severity of periodontal disease in SLE patients and the sub gingival levels of different pathogens. A total of 60 women attending of Brasília University Hospital, aged 18-65 years, were invited to participate in the study. SLE patients were allocated in two subgroups according with disease activity: SLE-A (active disease; n= 31) and SLE-I (inactive disease; n= 29). A number of 31 systemically healthy women at the same age range composed control group. Patients were clinically examined according to probing depth (PD), clinical attachment level (CAL), sulcular bleeding index (SBI) and plaque index (PLI) at baseline examination. Sub gingival biofilm samples were collected from the deepest four sites before periodontal treatment in order to identify and quantify the level of periodontopathogens by checkerboard DNA-DNA hybridization. No significant differences were found between groups in PD, CAL and PLI. Significant differences were observed in GBI between SLE-A (11,19% ± 14,62%) compared to controls (17,30% ± 14.88%), although with no differences when compared to SLE-I (11,34% ± 11,59%). There was a low prevalence of PD and attachment loss 4 mm at all groups. A low prevalence of Actinomyces was observed at all groups, with an increase in red complex species at LES-I (4,07 x 105; 95% CI: 0,16-0,79) compared to control (2,50 x 105; 95% CI: 1,23-3,77), although with significant differences (p< 0,05; Kruskal Wallis post hoc Dunn) only when compared to SLE-A (0,45 x 105; 95% CI: 0,16-0,79). These findings show no differences in the periodontal conditions of SLE compared to systemically healthy patients, except for a decrease in gingival bleeding index, especially at SLE-A. Reductions in microorganisms count were observed at SLE-A, while an increase in bacterial count, especially at red and green complex, were observed at subgingival biofilm of SLE-I patients.