Introdução: O lúpus eritematoso sistêmico (LES) é uma doença autoimune caracterizada por uma alteração no sistema imunológico e uma inflamação crônica. O exercício físico agudo e crônico têm sido apontados como uma estratégia capaz de atenuar os acometimentos da doença e os fatores de risco cardiovasculares em pacientes com LES. Entretanto, ainda não se sabe se o exercício físico poderia piorar o quadro inflamatório e imunológico de pacientes com LES em remissão (LESREM) e atividade da doença (LESATIV). Objetivos: Avaliar o efeito agudo e crônico do exercício aeróbio na resposta das citocinas (IFN-y, IL-10, IL-6 e TNF-alfa) e receptores solúveis de TNF (sTNFR1 e sTNFR2) séricos e na expressão gênica em leucócitos circulantes de pacientes com LESREM e LESATIV. Métodos: A resposta das citocinas e dos sTNFRs às sessões agudas de exercício moderado (~50% do VO2pico) e intenso (~70% do VO2pico) foram avaliadas em 11 pacientes com LESATIV, 12 pacientes com LESREM e 10 controles saudáveis (GC), os quais foram pareados por sexo, idade e índice de massa corporal. A resposta da expressão gênica em leucócitos circulantes à sessão aguda intensa de exercício foi avaliada em quatro voluntárias por grupo (LESATIV, LESREM e GC). O treinamento aeróbio (12 semanas, 2x/semana, 30 a 50 minutos, FC entre os limiares ventilatórios) foi realizado por oito pacientes com LESREM. As citocinas e os sTNFRs foram avaliados por multiplex e a expressão gênica pelo método de PCRarray, com subsequente análise bioinformática. Resultados: Em resposta a sessão aguda moderada de exercício não houve alteração na resposta das citocinas e receptores solúveis de TNF (P > 0,05), com exceção da redução da IL-6 e do sTNFR1 na recuperação nos grupos LESATIV e GC (P < 0,05), respectivamente. Após o exercício agudo intenso, apenas o sTNFR1 reduziu durante a recuperação (P < 0,05) no grupo LESREM. No GC, a IL-10, o TNF-alfa, o sTNFR1 e o sTNFR2 permaneceram inalterados (P > 0,05), enquanto o IFN-y reduziu ao final do exercício (P = 0,05) e a IL-6 apresentou um aumento transitório ao final do exercício (P = 0,028). No grupo LESATIV, houve um aumento transitório da IL-10, IL-6 e TNF-alfa (P < 0,05), porém, todos os valores estavam normalizados 24 horas após o término da sessão. A análise da expressão gênica mostrou que uma sessão aguda de exercício intenso pode modular a expressão de genes nos leucócitos circulantes. Ao final da sessão intensa de exercício, houve uma redução da expressão de genes relacionados a citocinas e seus receptores, bem como da via dos receptores do tipo toll e da JAK/STAT nos três grupos do estudo, porém, com uma menor quantidade de genes alterados nos grupos LESREM e LESATIV comparados ao GC. Em resposta ao treinamento aeróbio, o grupo LESREM apresentou uma redução da concentração basal do sTNFR2 (P = 0,025) e uma tendência para redução da IL-10 (P = 0,093). Além disso, a área sob a curva (ASC) da resposta da cinética da IL-10 às sessões agudas moderada e intensa de exercício reduziram após o treinamento aeróbio (P < 0,05). As ASCs da IL-10, IL-6, TNF-alfa e sTNFR1 em resposta a sessão moderada de exercício não reduziram, mas alcançaram os valores do GC (P > 0,05). Conclusão: As sessões agudas de exercício moderado e intenso não exacerbam o quadro inflamatório em pacientes com LESREM e LESATIV. Adicionalmente, uma sessão intensa de exercício parece modular a expressão gênica em leucócitos circulantes de pacientes com LESREM e LESATIV, porém, em menor quantidade comparados ao GC. Por fim, o treinamento aeróbio parece reduzir o milieu inflamatório em pacientes com LESREM / Background: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by an altered immune system and a chronic inflammation. Acute and chronic physical exercise has been emerged as a strategy to attenuate the disease outcomes and the cardiovascular risk factors in SLE patients. However, it is not known yet if physical exercise could dysregulate the inflammatory process and immune system in active (SLEACTIVE) and inactive SLE patients (SLEINACTIVE). Aims: to assess the effects of acute and chronic aerobic exercise training on the serum cytokines (IFN-y, IL-10, IL-6 e TNF-?) and soluble TNF receptors (sTNFR1 and sTNFR2) levels and in the gene expression of circulating leukocytes in SLEACTIVE and SLEINACTIVE patients. Methods: Cytokines and sTNFRs responses to acute moderate (~50% of VO2peak) and intense (~70% of VO2peak) aerobic exercise were assessed in 11 SLEACTIVE patients, 12 SLEINACTIVE patients and 10 healthy controls (HC), who were matched for age, sex and body mass index. Leucocytes gene expression responses to acute intense exercise were assessed in four subjects of each group (SLEACTIVE, SLEINACTIVE, and HC). Aerobic exercise training (12 weeks, twice a week, 30 to 50 minutes, HR between ventilatory thresholds) was performed by eight SLEINACTIVE patients. Cytokines and sTNFRs were assessed by multiplex technique and the gene expression by a PCRarray method, followed by bioinformatics analysis. Results: In response to an acute moderate exercise there were no significant differences in cytokines and sTNFRs (P > 0.05), except for the reduction in IL-6 and sTNFR1 during recovery in SLEACTIVE and HC (P < 0.05), respectively. After acute intense exercise, only sTNFR1 levels reduced during recovery (P < 0.05) in the SLEINACTIVE. In HC group, IL-10, TNF-?, sTNFR1 and sTNFR2 remained unchanged (P > 0.05), while IFN-y reduced at the end of exercise (P = 0.05) and IL-6 increased transitorily at the end of exercise (P = 0.028). In the SLEACTIVE group, there was a transitory increase in IL-10, IL-6 and TNF-alfa (P < 0.05), however, all cytokines were normalized 24 hours after the end of exercise. The analyses of gene expression showed that an acute intense aerobic exercise can modulate the gene expression in circulating leukocytes. At the end of acute intense exercise, there was a down-regulation of cytokines-cytokines receptor genes, and in the genes involved in the toll-like receptors and JAK/STAT pathways, however, with fewer genes altered in the SLEACTIVE and SLEINACTIVE groups compared with HC. In response to aerobic exercise training, SLEINACTIVE showed a reduction in the baseline sTNFR2 levels (P = 0.025) and a tendency to decrease in IL-10 levels (P = 0.093). Moreover, area under the curve (AUC) of the IL-10 kinetics to acute moderate and intense aerobic exercise reduced after the aerobic exercise training (P < 0.05). The AUCs of IL-10, IL-6, TNF-alfa and sTNFR1 in response to acute moderate exercise did not reduce, but reached the HC values (P > 0.05). Conclusion: Acute moderate and intense aerobic exercise did not exacerbate the inflammatory process in SLEINACTIVE and SLEACTIVE patients. Additionally, acute intense aerobic exercise seems to modulate the gene expression in leukocytes of SLEINACTIVE and SLEACTIVE patients, however, in fewer genes than in HC group. Finally, the aerobic exercise training seems to reduce milieu inflammatory in SLEINACTIVE patients

Objetivo: Avaliar a antropometria do pênis em pacientes com lúpus eritematoso sistêmico (LES) e controles. A possível influência da puberdade e dos fatores clínicos, hormonais e terapêuticos nas mediadas penianas em pacientes lúpicos. Métodos: Vinte e cinco pacientes consecutivos com LES foram avaliados através de exame urológico, ultrassonografia testicular com Doppler, dosagem hormonal [folículo estimulante (FSH), hormônio luteinizante (LH), prolactina, dosagem total de testosterona pela manhã e inibina B] e análise genética (síndrome Klinefelter e microdeleção do cromossomo Y). Comprimento do pênis foi medido como a distância linear ao longo do lado dorsal do pênis que se estende desde a junção da pele pubopeniana à ponta da glande no estado flácido, enquanto que a circunferência do pênis foi medida no ponto médio do eixo. As características clínicas, SLEDAI, SLICC / ACR-DI, e tratamento também foram avaliados. O grupo controle incluiu 25 homens de idade comparável e saudáveis. Resultados: Pacientes com LES tiveram o comprimento médio do pênis e da sua circunferência significantemente menor, em comparação aos controles [8 (7,5-10) vs. 10 (8-13) cm, p=0,0001; 8 (7-10) vs. 10 cm (11/07) , p=0,001; respectivamente], e mediana do volume testicular direito e esquerdo por Prader [15 (10-25) vs. 20 (12-25) cm, p=0,003; 15 (25/10) vs. 20 (12-25) cm, p=0,006, respectivamente], maior mediana de FSH [5,8 (2,1- 25) vs. 3,3 (1,9-9) UI/l, p=0,002] e menores níveis de testosterona total, dosados pela manhã (28% versus 0%, p = 0,009 ) quando comparados aos controles. Apesar desses achados, a disfunção erétil não foi observada nos pacientes ou controles. Outras análises revelaram que a mediana da circunferência do pênis foi menor nos pacientes com LES que tiveram o início da doença antes da primeira ejaculação [7,8 (7-10) vs. 9,0 (7,5-10) cm, p=0,026] em comparação com aqueles que começaram a doença após a primeira ejaculação. Antropometria do pênis no lúpus não esteve relacionado aos baixos níveis de testosterona total (p=0,662), ao SLEDAI 4 (p=0,562), SLICC / ACR-DI 1 (p=0,478), nem a dose cumulativa de prednisona (p=0,789), ou ciclofosfamida endovenosa (p=0,754). Síndrome de Klinefelter (46XY/47XXY) foi diagnosticada em apenas um (4%) paciente com LES, e este apresentava diminuição do tamanho do pênis. Já a microdeleção do cromossomo Y esteve ausente em todos eles. Conclusões: Nós identificamos redução das dimensões do pênis em pacientes com LES sem efeito deletério na função erétil. A diminuição da circunferência do pênis esteve associada ao início da doença antes da espermarca. / Objective: The aim of this study was to evaluate penile anthropometry in systemic lupus erythematosus (SLE) patients compared with healthy controls and the possible relevant pubertal, clinical,hormonal and treatment factors that could influence penile dimensions. Methods: Twenty-five consecutive SLE patients were assessed by urological examination, sexual function, testicular ultrasound, hormones, sperm analysis, genetic analysis, clinical features and treatment. The control group included 25 age-matched healthy males. Results: SLE patients had a lower median penis length and circumference [8 (7.510) vs. 10 (813) cm, p=0.0001; 8 (710) vs. 10 (711) cm, p=0.001; respectively], lower median testicular volume by right and left Prader [15 (1025) vs. 20 (1225) ml, p=0.003; 15 (1025) vs. 20 (1225) ml, p=0.006; respectively], higher median of follicle-stimulating hormone [5.8 (2.125) vs. 3.3 (1.99) IU/l, p¼0.002] and lower morning total testosterone levels (28% vs. 0%, p¼0.009) compared with controls. In spite of that, erectile dysfunction was not observed in patients or controls. Analyses of lupus patients revealed that the median penis circumference was lower in patients with disease onset before first ejaculation compared with those with disease onset after first ejaculation [7.8 (710) vs. 9.0 (7.510) cm, p=0.026]. No differences were observed in the median penile anthropometry regarding sexual dysfunction (p=0.610), lower morning total testosterone levels (p=0.662), oligo/azoospermia (p=0.705), SLE Disease Activity Index 4 (p=0.562), Systemic Lupus International Collaborating Clinics/ACR Damage Index 1 (p=0.478), prednisone cumulative dose (p=0.789) and intravenous cyclophosphamide therapy (p=0.754). Klinefelter´s syndrome (46XY/47XXY) was diagnosed in one (4%) SLE patient with decreased penile size whereas Y-chromosomal microdeletions was absent in all of them. Conclusion: we have identified reduced penile dimensions in SLE patients with no deleterious effect in erectile function. Disease onset before first ejaculation seems to affect penis development in pre-pubertal lupus.

Objetivo: Ao nosso conhecimento, não há estudos na literatura avaliando simultaneamente um grande número de autoanticorpos órgãoespecíficos, bem como a prevalência de doenças autoimunes órgãoespecíficas em populações com lúpus eritematoso sistêmico juvenil (LESJ) e dermatomiosite juvenil (DMJ). Portanto, o objetivo deste estudo foi avaliar autoanticorpos e doenças autoimunes órgão-específicas em pacientes com LESJ e DMJ. Métodos: Quarenta e um pacientes com LESJ e 41 com DMJ foram investigados para os autoanticorpos séricos associados com hepatite autoimune, cirrose biliar primária, diabetes melito tipo 1 (DM1), tireoidite autoimune, gastrite autoimune e doença celíaca. Pacientes com positividade para anticorpos órgão-específicos foram avaliados para a presença das respectivas doenças autoimunes órgão-específicas. Resultados: A média de idade ao diagnóstico foi significativamente maior em pacientes com LESJ em comparação com DMJ (10,3 ± 3,4 vs. 7,3 ± 3,1 anos, p=0,0001), enquanto a média de duração da doença foi similar em ambos os grupos (p=0,92). As freqüências de autoanticorpos órgão-específicos foram semelhantes nos pacientes com LESJ e DMJ (p>0,05). Notavelmente, uma alta prevalência de autoanticorpos relacionados a tireoidite autoimune e DM1 e foi observada em ambos os grupos (20% vs. 15%, p=0,77 e 24% vs. 15%, p=0,41, respectivamente). A elevada freqüência de fator antinúcleo - FAN (93% vs. 59%, p=0,0006), anti-DNA (61% vs. 2%, p<0,0001), anti-Ro (35% vs. 0%, p<0,0001 ), anti-Sm (p=0,01), anti-RNP (p=0,02), anti-La (p=0,03) e aCL IgG (p=0,001) foram observadas em pacientes com LESJ em comparação com DMJ. Doenças autoimunes órgão-específicas foram evidenciadas apenas em pacientes com LESJ (24% vs. 0%, p=0,13). Dois pacientes com LESJ apresentavam DM1 associada com tireoidite de Hashimoto e um terceiro paciente apresentava tireoidite subclínica. Outro paciente com LESJ preenchia diagnóstico de doença celíaca com base em anemia por deficiência de ferro, a presença de anticorpo anti-endomísio, biópsia duodenal compatível com doença celíaca e resposta a dieta livre de glúten. Conclusão: Doenças órgão-específicas foram observadas apenas em pacientes com LESJ e exigiram tratamento específico. A presença destes anticorpos sugere a avaliação de doenças órgão-específicas e um acompanhamento rigoroso destes pacientes / Objective: To our knowledge, no study has assessed simultaneously a large number of organ-specific autoantibodies, as well as the prevalence of organ-specific autoimmune diseases in juvenile systemic lupus erythematosus (JSLE) and juvenile dermatomyositis (JDM) populations. Therefore, the purpose of this study was to evaluate organ-specific autoantibodies and autoimmune diseases in JSLE and JDM patients. Methods: Forty-one JSLE and 41 JDM patients were investigated for serum autoantibodies associated with autoimmune hepatitis, primary biliary cirrhosis, type 1 diabetes mellitus (T1DM), autoimmune thyroiditis, autoimmune gastritis and celiac disease. Patients with positive organspecific antibodies were assessed for the presence of the respective organ-specific autoimmune diseases. Results: Mean age at diagnosis was significantly higher in JSLE compared to JDM patients (10.3±3.4 vs. 7.3±3.1years, p=0.0001), whereas the mean disease duration was similar in both groups (p=0.92). The frequencies of organ-specific autoantibodies were similar in JSLE and JDM patients (p>0.05). Of note, a high prevalence of autoantibodies related to T1DM and autoimmune thyroiditis were observed in both groups (20% vs. 15%, p=0.77 and 24% vs. 15%, p=0.41; respectively). Higher frequencies of antinuclear antibody - ANA (93% vs. 59%, p=0.0006), anti-dsDNA (61% vs. 2%, p<0.0001), anti-Ro (35% vs. 0%, p<0.0001), anti-Sm (p=0.01), anti-RNP (p=0.02), anti-La (p=0.03) and IgG aCL (p=0.001) were observed in JSLE compared to JDM patients. Organ-specific autoimmune diseases were evidenced only in JSLE patients (24% vs. 0%, p=0.13). Two JSLE patients had T1DM associated with Hashimoto thyroiditis and another had subclinical thyroiditis. Another JSLE patient had celiac disease diagnosis based on iron deficiency anaemia, presence of anti-endomysial antibody, duodenal biopsy compatible to celiac disease and response to a gluten-free diet. Conclusion: Organ-specific diseases were observed solely in JSLE patients and required specific therapy. The presence of these antibodies recommends the evaluation of organ-specific diseases and a rigorous follow-up of these patients

O Lúpus Eritematoso Sistêmico (LES) é uma doença inflamatória crônica autoimune que apresenta uma ampla variedade de manifestações clínicas e anormalidades imunológicas, afetando principalmente mulheres. É caracterizado pela perturbação da homeostase imunológica, que envolve a indução e produção de autoanticorpos, bem como pela formação e deposição de complexos imunes, que conduzem a uma intensa resposta inflamatória e dano tecidual. Há evidências de que fatores imunológicos, ambientais, hormonais e genéticos estão implicados na patogênese da doença. Genes e proteínas envolvidas na metabolização/detoxificação de xenobióticos são frequentemente utilizados como marcadores de susceptibilidade para o desenvolvimento de doenças, cuja etiologia está relacionada à exposição a fatores de risco ambientais. Enzimas do Citocromo P450 (CYP) são as principais responsáveis pela fase I de detoxificação, na qual ativam o xenobiótico, tornando-o mais eletrofílico e, desta forma, mais reativo. As Glutationa S-transferases (GST) são enzimas detoxificantes de fase II e normalmente conjugam a glutationa reduzida com uma variedade de compostos eletrofílicos, como espécies reativas de oxigênio, facilitando a excreção de produtos tóxicos. Polimorfismos nos genes CYP e GST são capazes de alterar a expressão e a atividade catalítica das enzimas, sendo responsáveis por diferenças interindividuais quanto à capacidade de biotransformação de xenobióticos. O objetivo do nosso trabalho foi avaliar a influência de três polimorfismos GST (GSTM1 nulo, GSTT1 nulo, e GSTP1*Val) e dois polimorfismos CYP (CYP1A1*2C e CYP2E1*5B) na predisposição ao LES em uma amostra de 370 pacientes com LES e 329 doadores de sangue saudáveis provenientes da região sul do Brasil. Os polimorfismos CYP foram genotipados por PCR-RFLP, enquanto que os polimorfismos GST foram genotipados por PCR multiplex (GSTM1 nulo, GSTT1 nulo) e PCR-RFLP para GSTP1. As freqüências alélicas e genotípicas foram comparadas entre pacientes e controles usando o teste de Qui-Quadrado ou o teste Exato de Fisher. As análises foram realizadas subdividindo os indivíduos de acordo com sua origem étnica. Entre os indivíduos Euro-descendentes, observou-se uma menor freqüência de genótipos heterozigotos GSTP1*Val em pacientes com LES em comparação aos controles (p=0,0047; OR 0,63 CI 95% 0,43 – 0,93 em relação a GSTP1*Ile/Ile e OR 0,49 CI 95% 0,26 – 0,92 em relação a GSTP1*Val/Val). No grupo Afro-descendente, houve tendência a uma maior freqüência do alelo GSTP1*Val em pacientes quando comparados aos controles (p=0,061). O alelo CYP2E1*5B foi significativamente mais freqüente nos pacientes do que em controles (p=0,038; OR 2,69 CI 95% 1,00 – 8,42). Não foi observada qualquer implicação clínica dos polimorfismos CYP e GST nos pacientes com LES. Nossos dados sugerem um papel protetor do genótipo heterozigoto GSTP1*105Ile/Val em Euro-descendentes e uma possível influência do alelo CYP2E1*5B na susceptibilidade ao LES entre Afro-descendentes. / Systemic lupus erythematosus (SLE) is an autoimmune chronic inflammatory disease that presents a variety of clinical manifestations and immunological abnormalities, particularly affecting women. It is characterized by disruption of immunologic homeostasis, which results in the induction and production of autoantibodies, as well as the formation and deposition of immune complexes, leading to an intense inflammatory response and tissue damage. There is evidence that immunological, environmental, hormonal and genetic factors are involved in the pathogenesis of the disease. Genes and proteins involved in metabolism/detoxification of xenobiotics are often used as markers of susceptibility to the development of diseases whose etiology is related to exposure to environmental risk factors. Cytochrome P450 (CYP) enzymes are primarily responsible for phase I detoxification, in which activate the xenobiotic, making it more electrophilic and thus more reactive. The Glutathione S-transferases (GST) are phase II detoxifying enzymes and usually conjugate reduced glutathione with a variety of electrophilic compounds, such as reactive oxygen species, facilitating the excretion of toxic products. Polymorphisms in the CYP and GST genes can alter the expression and catalytic activity of enzymes, being responsible for interindividual differences regarding the capacity of xenobiotics biotransformation. The aim of our study was to evaluate the influence of three GST polymorphisms (GSTM1 null, GSTT1 null and GSTP1*Val) and two CYP polymorphisms (CYP1A1*2C and CYP2E1*5B) in SLE predisposition in a sample of 370 SLE patients and 329 healthy blood donors, both from southern Brazil. The CYP polymorphisms were genotyped by PCR-RFLP, while the GST polymorphisms were genotyped by multiplex PCR and PCR-RFLP for GSTP1. Allelic and genotypic frequencies were compared between patients and controls using the Chi-square test or Fisher´s exact test. Analyses were performed subdividing the individuals according to their ethnic origin. Among European-derived individuals, it was observed a lower frequency of GSTP1*Val heterozygous genotypes in SLE patients compared to controls (p = 0.0047; OR 0.63 CI 95% 0.43 - 0.93 in relation to GSTP1*Ile/Ile) and (OR 0.49 95% CI 0.26 - 0.92 in relation to GSTP1*Val/Val). In African-derived group, there was a trend to a higher frequency of GSTP1*Val allele in patients when compared to controls (p=0.061). The CYP2E1*5B allele was significantly more frequent in patients than controls (p=0.038, OR 2.69 95% CI 1.00 - 8.42). We did not observe any clinical implication of the CYP and GST polymorphisms in patients with SLE. Our data suggest a protective role of the GSTP1*105Ile/Val heterozygous genotype in European-derived and a possible influence of the CYP2E1*5B allele in SLE susceptibility among African-derived.

Introdução: A idade ao diagnóstico do lúpus eritematoso sistêmico juvenil (LESJ) pode influenciar a expressão da doença em termos de apresentação clínica inicial, padrão de envolvimento de órgãos e achados sorológicos. Objetivo: Avaliar dados demográficos, características clínicas e alterações laboratoriais no momento do diagnóstico da doença em três grupos etários diferentes de pacientes com LESJ: grupo A com início precoce (< 6 anos), grupo B com início em idade escolar ( >= 6 e < 12 anos) e grupo C com início em adolescentes ( >= 12 e < 18 anos). Métodos: Estudo multicêntrico brasileiro de coorte retrospectiva em 10 centros de reumatologia, incluindo 847 pacientes com o diagnóstico de LESJ. Resultados: Os pacientes foram divididos em três grupos: A com 39 (4%), B com 395 (47%) e C com 413 (49%). Dos 39 pacientes com LESJ do grupo A, 3 (8%) tinham < 2 anos, 4 (10%) >= 2 e < 3 anos e 32 (82%) >= 3 e < 6 anos. Setenta e quatro pacientes com LESJ foram analisados para os níveis séricos de C1q e a deficiência completa de C1q foi observada em 3/74 (4%), todos estes pertencentes ao grupo A. Os grupos foram semelhantes quanto às altas frequências de sexo feminino, nefrite, envolvimento neuropsiquiátrico, SLEDAI-2K ( >= 8), perfil de autoanticorpos, proteínas de fase aguda elevada e baixos níveis de complemento (p > 0,05). No entanto, as frequências de febre (78% vs. 61% vs. 47%, p < 0,0001), hepatomegalia (42% vs. 29% vs. 14%, p < 0,0001), esplenomegalia (28% vs. 12% vs. 4%, p < 0,0001) e lúpus discoide (13% vs. 4% vs. 4%, p=0,020) foram significantemente maiores no grupo A em comparação com os grupos B e C. As frequências de perda de peso > 2kg (19% vs. 28% vs. 36%, p < 0,017), fotossensibilidade (34% vs. 41% vs. 51% p < 0,006), leucopenia < 4.000/mm3 (14% vs. 25% vs. 30%, p=0,048) e linfopenia < 1.500/mm3 (22% vs. 41% vs. 47%, p=0,011) foram significantemente menores no grupo A. Conclusão: O presente estudo multicêntrico identificou que a apresentação inicial de LESJ foi caracterizada por alta frequência de envolvimento de órgãos internos nos três grupos estudados e algumas características clínicas e laboratoriais distintas nos grupos de início precoce e adolescentes / Introduction: Age at diagnosis of childhood-onset systemic lupus erythematosus (cSLE) may influence disease expression in terms of initial clinical presentation, pattern of organ involvement and serological findings. Objective: To evaluate demographic data, clinical and laboratory features at disease diagnosis in three different age groups of childhood systemic lupus erythematosus (cSLE): group A early-onset ( < 6 years), group B school age ( >= 6 and < 12 years) and group C adolescent ( >= 12 and < 18 years). Methods: Brazilian multicenter cohort retrospective study in 10 Pediatric Rheumatology centers, including 847 cSLE patients. Results: Patients were divided in three groups: A with 39 (4%), B 395 (47%) and C 413 (49%). Of 39 cSLE patients of group A, 3 (8%) were < 2 years, 4 (10%) >= 2 to < 3 years and 32 (82%) >= 3 and < 6 years. Seventy-four cSLE patients were analyzed for C1q levels and complete C1q deficiency was observed in 3/74 (4%), all of them of group A. Groups were similar regarding high frequencies of female gender, nephritis, neuropsychiatric involvement, SLEDAI-2K ( >= 8), autoantibody profile, elevated acute phase proteins and low complement levels (p > 0.05). However, the frequency of fever (78% vs. 61% vs. 47%, p < 0.0001), hepatomegaly (42% vs. 29% vs. 14%, p < 0.0001), splenomegaly (28% vs. 12% vs. 4%, p < 0.0001) and discoid lupus (13% vs. 4% vs. 4%, p=0.020) was significantly higher in the group A compared to groups B and C. The frequency of weight loss > 2kg (19% vs. 28% vs. 36%, p=0.017), photosensitivity (34% vs. 41% vs. 51%, p=0.006), leukopenia < 4,000/mm3 (14% vs. 25% vs. 30%, p=0.048) and lymphopenia < 1,500/mm3 (22% vs. 41% vs. 47%, p=0.011) was significantly lower in the group A. Conclusions: Our large multicenter study identified that the initial presentation of cSLE is characterized by comparable high frequency of internal organ involvement and some distinct clinical and laboratory features in early-onset and adolescent groups

This research study explored the experiences of 19 women who had been diagnosed with, or were still seeking the diagnosis of SLE (lupus) and their decisions regarding support group participation. The aim of this study was to evaluate the variety of factors influencing their choices in types and sources of support, their coping strategies and the reasons behind their decisions to either choose or not choose lupus support groups as a viable support resource. Those women identified as support groups attendees recalled a more emotion-focused response to their diagnosis and showed stronger reliance on seeking emotional forms of support. Conversely, those women who chose not to participate in groups (non-attendees) utilized more problem-focused strategies when they received their news of the illness and indicated more reliance on instrumental forms of support. Additionally, the women who do not attend support groups did not seem to have more social support from outside sources, but did show a tendency to utilize relationship-focused coping more than other forms of coping strategies overall. Both groups showed a heavy reliance on their medical providers for both emotional and instrumental forms of support suggesting this source as an important factor in individual choices in coping strategies and support sources. The decisions to attend or not attend differed only in the strategies they relied on and specific group structure, timing and locations. The results of this study supports earlier research in the types and sources of social support used in adapting to a chronic illness. This study also encourages incorporating individual support services through medical providers and the development of programs that acknowledge individual coping and support needs.

Bibliography: leaves 99-106.

<p>Single nucleotide polymorphisms (SNPs) are the most common form of genetic variation. We developed a novel multiplexed method for SNP genotyping based on four-color fluorophore tag-microarray minisequencing. This method allows simultaneous genotyping of 80 samples and up to 200 SNPs in any allele combination. In study I we set up the method for a panel of SNPs from genes in the type I interferon system, and applied it in study III. In study II we used the technique to genotype SNPs from the coding region of the mitochondrial genome. A panel of 150 SNPs was genotyped in 265 individuals representing nine different populations. We demonstrated that the multiplexed SNP genotyping method for mitochondrial DNA increases the power of forensic identification in combination with sequencing of the hypervariable region of mitochondrial DNA. </p><p>In study III we performed a genetic association study of SNPs in genes related to the type I Interferon system in Systemic Lupus Erythematosus (SLE). SLE is a chronic autoimmune inflammatory disease with a complex etiology. The SNPs were genotyped in DNA samples from Swedish, Finnish, and Icelandic patients with SLE, unaffected family members, and unrelated controls. The analysis identified SNPs in two genes, the tyrosine kinase 2 (TYK2) and interferon regulatory factor 5 (IRF5) genes that are highly associated with SLE with p-values <10^-7 for joint linkage and association. </p><p>Study IV describes the analysis of the TYK2 and IRF5 SNPs in a large Rheumatoid Arthritis (RA) sample cohort. We found that SNPs in the IRF5 gene were significantly associated with RA with a p-value = 0.00008. In contrast, we did not detect an association with SNPs in the TYK2 gene. These findings demonstrate that SLE and RA may have a common genetic background in the case of IRF5, while the TYK2 variants appear to be unique for SLE. </p>

Single nucleotide polymorphisms (SNPs) are the most common form of genetic variation. We developed a novel multiplexed method for SNP genotyping based on four-color fluorophore tag-microarray minisequencing. This method allows simultaneous genotyping of 80 samples and up to 200 SNPs in any allele combination. In study I we set up the method for a panel of SNPs from genes in the type I interferon system, and applied it in study III. In study II we used the technique to genotype SNPs from the coding region of the mitochondrial genome. A panel of 150 SNPs was genotyped in 265 individuals representing nine different populations. We demonstrated that the multiplexed SNP genotyping method for mitochondrial DNA increases the power of forensic identification in combination with sequencing of the hypervariable region of mitochondrial DNA. In study III we performed a genetic association study of SNPs in genes related to the type I Interferon system in Systemic Lupus Erythematosus (SLE). SLE is a chronic autoimmune inflammatory disease with a complex etiology. The SNPs were genotyped in DNA samples from Swedish, Finnish, and Icelandic patients with SLE, unaffected family members, and unrelated controls. The analysis identified SNPs in two genes, the tyrosine kinase 2 (TYK2) and interferon regulatory factor 5 (IRF5) genes that are highly associated with SLE with p-values &lt;10-7 for joint linkage and association. Study IV describes the analysis of the TYK2 and IRF5 SNPs in a large Rheumatoid Arthritis (RA) sample cohort. We found that SNPs in the IRF5 gene were significantly associated with RA with a p-value = 0.00008. In contrast, we did not detect an association with SNPs in the TYK2 gene. These findings demonstrate that SLE and RA may have a common genetic background in the case of IRF5, while the TYK2 variants appear to be unique for SLE.

Pre-eclampsia is associated with increased risk of cardiovascular disease (CVD) later in life. The ‘gold standard’ for estimating cardiovascular risk - ultrasound assessment of the common carotid artery intima-media thickness (CCA-IMT) - does not convincingly demonstrate this increased risk. The aim of this thesis was to examine whether high-frequency (22 MHz) ultrasound assessment of the individual CCA intima and media layers and calculation of the intima/media (I/M) ratio - can indicate the increased cardiovascular risk after pre-eclampsia. After validation of the method in premenopausal women with systemic lupus erythematosus (SLE) who have a recognized increased risk of CVD, women during and after normal and preeclamptic pregnancies were investigated. Assessment of the individual artery wall layers reliably demonstrated the increased cardiovascular risk in premenopausal women with SLE, while CCA-IMT did not. The artery wall layer dimensions in women with SLE were comparable to those of postmenopausal women without SLE and were 30 years older. Among the women with normal pregnancies negative changes to the artery wall later on in the pregnancy were seen in those with lower serum estradiol, older age, higher body mass index or higher blood pressure early in the pregnancy. About one year postpartum, both the mean intima thickness and the I/M ratio had improved, compared to values during pregnancy. These findings support the theory that normal pregnancy is a stress on the vascular system. Women who developed pre-eclampsia (mean age 31 years) had thicker intima layers, thinner media layers and higher I/M ratios, both at diagnosis and one year postpartum, than women with normal pregnancies, indicating increased cardiovascular risk. Women with a history of severe pre-eclampsia (mean age 44 years; mean 11 years since the last delivery) had thicker intima layers and higher I/M ratios than women with a history of normal pregnancies, indicating long-standing negative vascular effects. Assessment of individual CCA wall layers, but not of CCA-IMT, provided clear evidence of the well-known increased cardiovascular risk in women with SLE or pre-eclampsia. The method has the potential to become an important tool in reducing cardiovascular morbidity and mortality in these women through early diagnosis and intervention.