Increased Fas and Bcl-2 Expression on Peripheral Blood T and B Lymphocytes from Juvenile-Onset Systemic Lupus Erythematosus, but not from Juvenile Rheumatoid Arthritis and Juvenile Dermatomyositis

Defective regulation of apoptosis may play a role in the development of autoimmune diseases. Fas and Bcl-2 proteins are involved in the control of apoptosis. The aims of this study were to determine the expression of Fas antigen and Bcl-2 protein on peripheral blood T and B lymphocytes from patients with juvenile-onset systemic lupus erythematosus (JSLE), juvenile rheumatoid arthritis (JRA) and juvenile dermatomyositis (JDM). Thirty-eight patients with JSLE, 19 patients with JRA, 10 patients with JDM and 25 healthy controls entered the study. Freshly isolated peripheral blood mononuclear cells (PBMC) were stained for lymphocyte markers CD3, CD4, CD8, CD19 and for Fas and Bcl-2 molecules. Expressions were measured by three-color flow cytometry. Statistical analysis was performed using Kruskal–Wallis test. Percentages of freshly isolated T lymphocytes positively stained for Fas protein from JSLE patients were significantly increased compared to healthy controls, patients with JRA and patients with JDM. Percentages of B lymphocytes positive for Fas from JSLE patients were higher than healthy controls and JRA patients. In addition, Fas expression on T cells from patients with JRA was increased compared to JDM patients. Otherwise, Fas expression on T and B cells from JRA and JDM patients were similar to healthy controls. MFI of Bcl-2 positive T lymphocytes from JSLE patients were significantly increased compared to healthy controls and JRA patients. MFI of Bcl-2 protein on B lymphocytes from JSLE patients was similar to healthy controls and patients with JRA and JDM. Bcl-2 expression did not differ between JRA and JDM patients and healthy controls. In conclusion, increased expression of Fas and Bcl-2 proteins observed in circulating T and B lymphocytes from patients with JSLE, but not from patients with JRA and JDM, suggests that abnormalities of apoptosis may be related to the pathogenesis of JSLE and probably are not a result of chronic inflammation

Anticorpos anti-célula-endothelial e envolvimento do sistema nervoso central na moléstia de Behçet

INTRODUCTION: Previous studies have detected the presence of anti-endothelial cell antibodies (AECA) in patients with Behçet's disease (BD). However, no real evidence exists whether these antibodies exert any influence on clinical presentation and/or activity of this disease. OBJECTIVES: To determine the frequency of AECA in patients with BD and analyze possible clinical associations. METHODS: 50 patients with BD who fulfilled diagnostic criteria were selected. Thirty-seven patients were females, and 13 were males; the mean age was 44 ± 9 years with a mean follow-up time of 10 ± 7.5 years. AECA were assayed by ELISA using ECV-304 cells as the antigenic substrate. The prevalence of AECA was determined, and their possible relationships with present and past clinical features were investigated. RESULTS: AECA were detected in the sera of 38% of the patients (IgG in 13, IgM in four, and IgG plus IgM in two). An association was observed between AECA and a previous history of central nervous system involvement (OR= 5.4, p= 0.03). This association was more evident for IgG-AECA (OR= 6.0, p= 0.02). A trend of an increased risk of aneurysms was also observed in patients with IgG-AECA (OR= 2.58, p= 0.77). None of the other clinical characteristics showed a relevant association with these antibodies. CONCLUSION: Our data suggest that IgG-AECA may be a marker of more severe lesions in patients with BD based on the higher frequency of previous central nervous system manifestations in patients who presently display circulating AECA.INTRODUÇÃO: Estudos anteriores detectaram a presence de anticorpos anti-célula endotelial (AACE) em pacientes com doença de Behçet, porém não há nenhuma evidência se a presença destes anticorpos exerce alguma influência na apresentação clínica ou atividade da doença. OBJETIVOS: Determinar a freqüência de AACE em pacientes com doença de Behçet e analisar possíveis associações clínicas. MÉTODOS: Foram selecionados 50 pacientes que preencheram corretamente os critérios diagnósticos para a doença de Behçet. Trinta e sete pacientes eram do sexo feminino e 13 do sexo masculino, média de idade de 44 ± 9 anos e tempo médio de seguimento de 10 ± 7,5 anos. O AACE foram analisados por ELISA utilizando células ECV-304 como substrato antigênico. A prevalência de AACE foi determinada e foram investigadas possíveis relações com características clínicas atuais e pregressas. RESULTADOS: Os AACE foram detectados no soro de 38% dos pacientes (13 na forma IgG, 4 IgM e 2 nas formas IgG e IgM). Observamos uma associação entre o AACE e história pregressa de envolvimento de sistema nervoso central (OR=5,4; p=0,03). Esta associação era mais evidente para o AACE na forma IgG (OR=6,0; p=0,02). Observamos também uma tendência de risco aumentado de aneurismas em pacientes com AACE na forma IgG (OR=2,58; p=0,77). Nenhuma outra característica clínica mostrou-se relevante com o anticorpo estudado. CONCLUSÃO: Nossos dados sugerem que o AACE na forma IgG pode ser uma marcador de lesão mais grave em pacientes com doença de Behçet baseado no fato de encontrarmos uma maior freqüência de história pregressa de manifestação de sistema nervoso central em pacientes com AACE circulante

Decreased high-density lipoprotein cholesterol levels in polyarticular juvenile idiopathic arthritis

OBJECTIVES: To investigate the prevalence of dyslipoproteinemia in a homogeneous cohort of polyarticular juvenile idiopathic arthritis patients. METHODS: Based on the National Cholesterol Education Program, fasting lipoprotein levels and risk levels for coronary artery disease were determined in 28 patients with polyarticular juvenile idiopathic arthritis. The exclusion criteria included diabetes, thyroid dysfunction, smoking, proteinuria, lipid-lowering drugs, and hormone/diuretic therapy. Disease activity, disease duration, and therapy with corticosteroids and/or chloroquine were defined at the time of lipid measurements. RESULTS: Dyslipoproteinemia was identified in 20 of the 28 (71%) patients with polyarticular juvenile idiopathic arthritis. The primary lipoprotein risk factor was decreased high-density lipoprotein cholesterol (57%), followed by elevated levels of low-density lipoprotein cholesterol (18%), triglycerides (14%), and total cholesterol (7%). The male patients had decreased high-density lipoprotein cholesterol levels than the female patients (p<0.05). The incidence of decreased high-density lipoprotein cholesterol levels did not seem to be affected by disease activity or therapy because the incidence was similar in patients with active or inactive disease, with or without corticosteroid use and with or without chloroquine use. In addition, the frequency of decreased high-density lipoprotein cholesterol levels was similar in patients with short (&#8804;5 years) vs. long (>5 years) disease duration. CONCLUSIONS: Dyslipoproteinemia is highly prevalent in patients with polyarticular juvenile idiopathic arthritis and is primarily related to decreased high-density lipoprotein cholesterol levels; therefore, early intervention is essential

Rastreamento da infecção latente por tuberculose em pacientes com artrite idiopática juvenil previamente à terapia anti‐TNF em um país de alto risco para tuberculose

ResumoObjetivoAvaliar, em um país endêmico, a eficácia em longo prazo do rastreamento à procura de infecção latente por tuberculose (ILTB) e profilaxia primária em pacientes com AIJ em uso de bloqueadores do TNF.MétodosTrata‐se de uma coorte retrospectiva que incluiu pacientes com AIJ elegíveis para a terapia anti‐TNF. Os pacientes foram rastreados à procura de ILTB previamente ao uso de anti‐TNF por meio do teste tuberculínico (TT), radiografia de tórax e história de exposição à TB. Os indivíduos foram acompanhados regularmente em intervalos de dois meses.ResultadosIncluíram‐se 69 pacientes com AIJ com idade atual de 17,4±5,8 anos, com média de duração da doença de 5±4,9 anos; 47 pacientes receberam um único anti‐TNF, enquanto 22 foram transferidos para outro anti‐TNF uma ou duas vezes: 57 foram tratados com etanercepte, 33 com adalimumabe e três com infliximabe. O rastreamento à procura de ILTB foi positivo em três pacientes: um era TT positivo e tinha história de exposição à TB e dois apenas eram TT positivo. Não foi diagnosticado caso de TB ativa durante o período de estudo (mediana de seguimento de 3,8 anos).ConclusãoA avaliação em longo prazo revelou que o rastreamento à procura de ILTB e a profilaxia primária antes do tratamento com anti‐TNF foram eficazes em um país de alto risco para TB e o TT foi o parâmetro mais sensível para identificar esses pacientes.AbstractObjectivesTo evaluate, in an endemic country, the long‐term efficacy of latent tuberculosis infection (LTBI) screening and primary prophylaxis in patients with JIA receiving TNF blockers.MethodsThis was a retrospective cohort that included JIA patients eligible to anti‐TNF therapy. Patients were screened for LTBI prior to anti‐TNF using tuberculin skin test (TST), chest X‐ray and history of exposure to TB. Subjects were regularly followed at 2‐month intervals.ResultsSixty‐nine JIA patients with current age of 17.4±5.8 years, mean disease duration of 5.0±4.9 years were included. Forty‐seven patients received a single anti‐TNF, while 22 patients switched to another anti‐TNF once or twice: 57 were treated with etanercepte, 33 patients with adalimumab and 3 infliximab. LTBI screening was positive in three patients: one had TST‐positive and history of TB exposure and two had solely TST‐positive. No active TB was diagnosed during the study period (median of follow‐up was 3.8 years).ConclusionLong‐term evaluation revealed that LTBI screening and primary prophylaxis before anti‐TNF treatment was effective in a high‐risk country and TST was the most sensitive parameter to identify these patients

Anti-endothelial cell antibodies and central nervous system involvement in Behçet's disease

INTRODUCTION: Previous studies have detected the presence of anti-endothelial cell antibodies (AECA) in patients with Behçet's disease (BD). However, no real evidence exists whether these antibodies exert any influence on clinical presentation and/or activity of this disease. OBJECTIVES: To determine the frequency of AECA in patients with BD and analyze possible clinical associations. METHODS: 50 patients with BD who fulfilled diagnostic criteria were selected. Thirty-seven patients were females, and 13 were males; the mean age was 44 &plusmn; 9 years with a mean follow-up time of 10 &plusmn; 7.5 years. AECA were assayed by ELISA using ECV-304 cells as the antigenic substrate. The prevalence of AECA was determined, and their possible relationships with present and past clinical features were investigated. RESULTS: AECA were detected in the sera of 38% of the patients (IgG in 13, IgM in four, and IgG plus IgM in two). An association was observed between AECA and a previous history of central nervous system involvement (OR= 5.4, p= 0.03). This association was more evident for IgG-AECA (OR= 6.0, p= 0.02). A trend of an increased risk of aneurysms was also observed in patients with IgG-AECA (OR= 2.58, p= 0.77). None of the other clinical characteristics showed a relevant association with these antibodies. CONCLUSION: Our data suggest that IgG-AECA may be a marker of more severe lesions in patients with BD based on the higher frequency of previous central nervous system manifestations in patients who presently display circulating AECA.INTRODUÇÃO: Estudos anteriores detectaram a presence de anticorpos anti-célula endotelial (AACE) em pacientes com doença de Behçet, porém não há nenhuma evidência se a presença destes anticorpos exerce alguma influência na apresentação clínica ou atividade da doença. OBJETIVOS: Determinar a freqüência de AACE em pacientes com doença de Behçet e analisar possíveis associações clínicas. MÉTODOS: Foram selecionados 50 pacientes que preencheram corretamente os critérios diagnósticos para a doença de Behçet. Trinta e sete pacientes eram do sexo feminino e 13 do sexo masculino, média de idade de 44 &plusmn; 9 anos e tempo médio de seguimento de 10 &plusmn; 7,5 anos. O AACE foram analisados por ELISA utilizando células ECV-304 como substrato antigênico. A prevalência de AACE foi determinada e foram investigadas possíveis relações com características clínicas atuais e pregressas. RESULTADOS: Os AACE foram detectados no soro de 38% dos pacientes (13 na forma IgG, 4 IgM e 2 nas formas IgG e IgM). Observamos uma associação entre o AACE e história pregressa de envolvimento de sistema nervoso central (OR=5,4; p=0,03). Esta associação era mais evidente para o AACE na forma IgG (OR=6,0; p=0,02). Observamos também uma tendência de risco aumentado de aneurismas em pacientes com AACE na forma IgG (OR=2,58; p=0,77). Nenhuma outra característica clínica mostrou-se relevante com o anticorpo estudado. CONCLUSÃO: Nossos dados sugerem que o AACE na forma IgG pode ser uma marcador de lesão mais grave em pacientes com doença de Behçet baseado no fato de encontrarmos uma maior freqüência de história pregressa de manifestação de sistema nervoso central em pacientes com AACE circulante

PReS-FINAL-2170: Work disability in adult patients with juvenile idiopathic arthritis (JIA)

Introduction Approximately 20% JIA patients enters adulthood with clinically active disease and disabled, therefore work condition may be affected. Objectives To assess the prevalence of work disability among adult patients with JIA regularly attending a tertiary heumatology center and to determine possible associated risk factors.\ud Methods This was a cross-sectional study that enrolled 43 JIA patients according to 2004 revised ILAR criteria. A questionnaire was developed in order to evaluate working status and labor activity: occupation, current/previous work, employment status and withdrawal rate were actively searched. Demographic data, JIA characteristics, clinical activity (DAS28>2.6), therapeutic intervention, comorbidities, physical activity, sedentarism (WHO definitions), functional class (1991 ACR criteria), HAQ and SF-36 were recorded. The prevalence of work disability was calculated using 95% confidence interval, and compared to all parameters; qualitative variables were analyzed using tests of association (chi-square test) and quantitative variables by Mann-Whitney or student test. Results\ud Patients' mean age was 29+7.4 yrs (range 19-41) with mean JIA duration = 17.2+12.3 yrs (range 3-33); 63% were males and 37% females. JIA subtypes were 64% polyarticular, 11% oligoarticular, 9% systemic, 9% ERA, 2% extended oligoarticular, 2% psoriatic arthritis; 7% had uveitis. Serum RF was positive in 21% and ANA in 21%. The majority (72%, n = 31) of JIA patients were employed, whereas 28% (n = 12) were currently not working. In the latter group, 83% (10/12) were retired due to JIA related disability. Further analysis comparing those currently working vs. Those not working revealed similar age (25,3 yrs vs.29,5 yrs, p = 0,09). Although not significantly, most patients currently working had Poly onset JIA (22 vs. 6 p = 0,37), higher frequencies of good education level >12 yrs of school (31 vs.9, p = 0,38), functional class I (p = 0,96), practiced regular physical activity (9 vs. 0, p = 0,89), were singles (26 vs. 8, p = 0,15). Both groups had comparable HAQ and DAS 28 scores (0,62 vs. 0.59, p = 0,47 and 2,51 vs.2,07, p = 0,64) and similar arthroplasty rate (8 vs. 4, p = 0,427). Frequencies of hypertension (3 vs.1, p = 0,999), dyslipidemia (1 vs. 1, p = 0,125), diabetes (1 vs. 0 p = 0,999), depression (1 vs. 0, p = 0,999) and smokers (3 vs. 1, p = 0,99) were alike in both groups. Remarkably, employed patients had higher SF 36 mental health component (84.0 vs. 70.42, P = 0.01). Conclusion\ud High prevalence of almost 1/3 work disability and of retirement due to disease related incapacity remain major problems for adult JIA individuals. We also identified worse mental health in employed patients indicating that further research is needed, in addition to intense affirmative disability actions in order to remove possible disabling barriers and to adapt restrictive environments for these patients. Moreover, enhanced strategies and policy for inclusion of JIA patients in the job market is urged