Longitudinal comparison of IL-6, IL-10, and IL-12 cytokine profiles in adult and childhood-onset systemic lupus erythematosus.

Objective: To compare the levels of Th1 (IL-12) and Th2 (IL-6 and IL10) cytokines over a two-year period among systemic lupus erythematosus patients with childhood-onset (cSLE), adult-onset (sSLE), and healthy controls, and correlate with their clinical, laboratory, and treatment manifestations. Methods: The study included 63 patients with cSLE [57 (90%) women; mean age 19.7 ± 4.3 years (range = 10-29); mean disease duration 7.3 ± 4.2 years (range 2-15)], 67 patients with aSLE [65 (97%) women; mean age of 39.9 ± 11.8 years (range 21-68); disease duration 7.7 ± 3.1 years (range 4-16)], and 40 healthy controls [36 (90%) women; mean age of 29.6 ± 10 years (range 12-49)]. cSLE and aSLE patients were paired by disease duration. Clinical and laboratory manifestations, disease activity (SLEDAI), cumulative damage (SDI), and current drug exposures were evaluated. Symptoms of anxiety and depression were evaluated by the Beck inventory (BAI and BDI, respectively). Th1 (IL-12) and Th2 (IL-6 and IL-10) cytokines were measured by the ELISA test. Data were collected at four different time points (TI, TII, TIII, and TIV) and compared by non-parametric tests. Results: IL-6 levels were significantly higher in aSLE patients compared to healthy controls at times I, II, and III (TI p = 0.013, TII p = 0.015, TIII p = 0.004, and TIV p = 0.634). However, no difference was observed between cSLE patients and healthy controls (TI p = 0.223, TII p = 0.613, TIII p = 0.341, and TIV p = 0.977). In addition, no difference was observed between aSLE and cSLE patients (TI p = 0.377, TII p = 0.123, TIII p = 0.105, and TIV p = 0.591). The levels of IL-12 were significantly higher in cSLE patients compared to healthy controls at all time points (TI p = 0.04, TII p < 0.001, TIII p = 0.015, and TIV p = 0.021). aSLE patients showed significantly elevated levels when compared to healthy controls at time III and IV (TI p = 0.752, TII p = 0.827, TIII p = 0.011*, and TIV p < 0.001*). cSLE patients showed significantly higher levels than aSLE patients at times I and II (TI p = 0.07*, TII p < 0.001*, TIII p = 0.998, and TIV p = 0.140). In aSLE patients, IL-6 was associated with headache (p = 0.006), arthritis (p = 0.044), and nephritis (p = 0.012); IL-10 was associated with nephritis (p = 0.043), hypocomplementemia (p = 0.001), and disease activity (p = 0.001); in these patients, IL-12 was associated with alopecia (p = 0.025) and leukopenia (p = 0.044). In cSLE patients, IL-6 was associated with arthritis (p = 0.022) and malar rash (p = 0.012). Conclusion: aSLE and cSLE patients with long disease duration present similar levels of cytokines, despite differences in clinical activity patterns over time.

Axonal dysfunction is associated with interferon-γ levels in childhood-onset systemic lupus erythematosus: a multivoxel magnetic resonance spectroscopy study.

OBJECTIVE: Axonal/neuronal damage has been shown to be a pathological finding that precedes neuropsychiatric manifestations in SLE. The objective of this study was to determine the presence of axonal dysfunction in childhood-onset SLE patients (cSLE) and to determine clinical, immunological and treatment features associated with its occurrence. METHODS: We included 86 consecutive cSLE patients [median age 17 (range 5-28) years] and 71 controls [median age 18 (5-28) years]. We performed proton magnetic resonance spectroscopic imaging using point resolved spectroscopy sequence over the superior-posterior region of the corpus callosum and signals from N-acetylaspartate (NAA), choline-based (CHO), creatine-containing (Cr), myo-inositol (mI), glutamate, glutamine and lactate were measured and metabolites/Cr ratios were determined. Complete clinical, laboratory and neurological evaluations were performed in all subjects. Serum IL-4, IL-5, IL-6, IL-10, IL-12, IL-17, TNF-α and INF-γ cytokine levels, antiribosomal P protein antibodies (anti-P) and S100ß were measured by ELISA using commercial kits. Data were compared by non-parametric tests. RESULTS: NAA/Cr ratios (P = 0.035) and lactate/Cr ratios (P = 0.019) were significantly decreased in cSLE patients when compared with controls. In multivariate analysis, IFN-γ levels [odds ratio (OR) = 4.1; 95% CI: 2.01, 7.9] and depressive symptoms (OR = 1.9; 95% CI: 1.1, 3.2) were associated with NAA/Cr ratio. Increased CHO/Cr was associated with the presence of cognitive impairment (OR = 3.4; 95% CI: 2.034, 5.078; P < 0.001). mI/Cr ratio correlated with cumulative glucocorticoids dosage (r = 0.361, P = 0.014). CONCLUSION: NAA and CHO ratios may be useful as biomarkers in neuropsychiatric cSLE. Longitudinal studies are necessary to determine whether they predict structural damage.

Trisomy X in a patient with childhood-onset systemic lupus erythematosus.

Childhood-onset systemic lupus erythematosus (cSLE) is a rare, chronic and systemic autoimmune disease generally with a more severe clinical phenotype than the adult-onset SLE. In both conditions, it is known that females are predominantly affected; therefore, the possible overlap of SLE and sex chromosomal abnormalities has attracted attention. Our case report describe the clinical manifestations and immunological profile of a Brazilian female with cSLE and trisomy X. The 22 year-old patient, diagnosed with cSLE at age of 11, present some features related to 47, XXX, such as difficulties at school and communication, although this was not enough to investigate for chromosome abnormalities. Cytoscan HD array screening allowed the comprehensive diagnosis for this patient. We also characterized her ancestral composition, showing that she has 6.2% higher African component than the mean from health subjects from the same geographical area. This report reinforces the role of the X chromosome dose effect for sex bias in SLE, as well as the importance of African ancestry composition in cLES. It also throws lights upon the application of high-throughput molecular analysis in a large scale cohort can be useful to detect the impact of the genomic findings for more accurate epidemiological data.

Familial Aggregation of Childhood- and Adulthood-Onset Systemic Lupus Erythematosus.

OBJECTIVE: To assess the familial occurrence of systemic lupus erythematosus (SLE) in a large Brazilian cohort. METHODS: Consecutive patients with SLE were recruited and stratified according to age at disease onset into childhood-onset SLE or adult-onset SLE. Each patient was personally interviewed regarding the history of SLE across 3 generations (first-, second-, and third-degree relatives). Recurrence rates were analyzed for each degree of relation. RESULTS: We included 392 patients with SLE (112 with childhood-onset SLE and 280 with adult-onset SLE). We identified 2,574 first-degree relatives, 5,490 second-degree relatives, and 6,805 third-degree relatives. In the combined overall SLE cohort, we observed a familial SLE recurrence rate of 19.4 in first-degree relatives, 5.4 in second-degree relatives, and 3.0 in third-degree relatives. Recurrence rates were higher for first- and second-degree relatives of patients with childhood-onset SLE than for first- and second-degree relatives of patients with adult-onset SLE (25.2 versus 18.4 for first-degree, and 8.5 versus 4.5 for second-degree), while in third-degree relatives, recurrence rates were higher in adult-onset SLE than in childhood-onset SLE (P = 2.2 × 10-4 for differences in recurrence proportions between childhood-onset SLE and adult-onset SLE). There were no phenotypic differences in patients from multicase versus single-case families, and there was no sex-skewing observed in the offspring of patients with SLE. CONCLUSION: The greater decline in SLE recurrence rate by generation in childhood-onset SLE versus adult-onset SLE suggests a more polygenic and epistatic inheritance and suggests that adult-onset SLE may be characterized by fewer risk factors that are individually stronger. This finding suggests a higher genetic load in childhood-onset SLE versus adult-onset SLE and a difference in the genetic architecture of the disease based on age at onset.

Sleep disorders in primary antiphospholipid syndrome.

The objective of this study was to evaluate the sleep quality, the presence of sleep disorders in patients with primary antiphospholipid syndrome (pAPS), and their possible clinical and laboratory associations. This was a cross-sectional study of 40 consecutive pAPS patients and 211 healthy age- and sex-matched controls. Demographic and clinical data, drug use, and antiphospholipid antibodies were evaluated. Sleep was evaluated using the Pittsburgh Sleep Quality Index (PSQI). pAPS patients had significantly worse sleep quality than healthy controls. Analyzing the individual components, pAPS had worse scores in five of seven components: sleep duration (p = 0.002), habitual sleep efficiency (p = 0.003), sleep disturbance (p < 0.001), use of sleep medication (p < 0.001), and daytime somnolence (p = 0.03). No association of sleep disturbance and demographic, clinical, and laboratory features of the disease was observed. This is the first study to analyze sleep quality in pAPS. We observed that pAPS had significant worse sleep quality; however, no demographic, clinical, or laboratory feature was associated with sleep disturbance.

Olfactory function in systemic lupus erythematosus and systemic sclerosis. A longitudinal study and review of the literature.

BACKGROUND/PURPOSE: To evaluate olfactory function in systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and healthy controls over a 2-year period, and to determine the association of olfactory dysfunction with age, disease activity, disease damage, treatment, anxiety and depression symptoms and limbic structures volumes. METHODS: Consecutive SLE and SSc patients were enrolled in this study. Clinical, laboratory disease activity and damage were assessed according to diseases specific guidelines. Olfactory functions were evaluated using the Sniffin' Sticks test (TDI). Volumetric magnetic resonance imaging (MRI) was obtained in a 3T Phillips scanner. Amygdalae and hippocampi volumes were analyzed using FreeSurfer® software. RESULTS: We included 143 SLE, 57 SSc and 166 healthy volunteers. Olfactory dysfunction was observed in 78 (54.5%) SLE, 35 (59.3%) SSc patients and in 24 (14.45%) controls (p<0.001) at study entry. SLE and SSc patients had significantly lower mean in all three phases (TDI) of the olfactory assessment when compared with healthy volunteers. In SLE, the presence of olfactory dysfunction was associated with older age, disease activity, higher anxiety and depression symptoms score, smaller left hippocampus volume, smaller left and right amygdalae volume and the presence of anti-ribosomal P (anti-P) antibodies. In SSc the presence of olfactory impairment was associated with older age, disease activity, smaller left and right hippocampi volumes and smaller right amygdala volume. Olfactory function was repeated after a 2-year period in 90 SLE, 35 SSc and 62 controls and was stable in all three groups. CONCLUSION: Both SLE and SSc patients with longstanding disease had significant reduction in all stages of TDI that maintained stable over a 2-year period. Olfactory dysfunction was associated with age, inflammation and hippocampi and amygdalae volumes. In SLE, additional association with anti-P, anxiety and depression symptoms was observed.

Defining biological subsets in systemic lupus erythematosus: progress toward personalized therapy.

Systemic lupus erythematosus (SLE) is a heterogeneous disease with respect to disease severity, response to treatment, and organ damage. The pathogenesis of SLE includes immunological mechanisms which are driven by both genetic and environmental factors. There are clear differences in the pathogenesis of SLE between patients of different ancestral backgrounds, including differences in genetic risk factors, immunological parameters, and clinical manifestations. Patients with high vs. low levels of type I interferon (IFN) in circulation represents one major biological subset within SLE, and these two groups of patients are present in all ancestral backgrounds. Genetic factors, autoantibodies, and levels of other cytokines all differ between high and low IFN patients. This distinction has also been important in predicting response to treatment with anti-type I IFN therapies, providing a precedent in SLE for biological subsets predicting treatment response. This review will highlight some recent developments in defining biological subsets of SLE based on disease pathophysiology, and the idea that improved knowledge of disease heterogeneity will inform our efforts to personalize therapy in this disease.

Assessment of condyle, masseter and temporal muscles volumes in patients with juvenile systemic lupus erythematosus: A cross-sectional study.

AIMS: The purpose of this study was to evaluate the effect of the corticosteroid therapy for both treatment of juvenile systemic lupus erythematosus and disease activity on two masticatory muscles and condyle of the temporomandibular joint. METHODS: A total of 21 controls and 48 juvenile systemic lupus erythematosus patients were investigated. Volumes of the temporal and masseter muscles and condyle of the subjects were assessed by using a 3D reconstruction in magnetic resonance imaging. The ITK-SNAP, a medical imaging software, was used for 3D reconstruction. A dental examination with registration of occlusion was performed in subjects. Data were statistically analyzed by means of the Dahlberg's test associated with paired t-test, Fisher's exact test and Chi-square. RESULTS: There was a positive correlation between temporalis muscle and age (p = 0.032), masseter volume (p = 0.029) and condyle volume (p = 0.013). The mean volume measurements of temporal and masseter muscles and condyle were not statistically associated with juvenile systemic lupus erythematosus regarding disease activity and corticosteroid therapy (p > 0.05). There were no significant differences between malocclusion and volume of muscles and condyle. CONCLUSION: This study suggested that volume of the target structures has no correlation with cumulative corticosteroid dose, disease activity, and malocclusion.

Prevalence and features of metabolic syndrome in childhood-onset systemic lupus erythematosus.

To estimate the prevalence and features of metabolic syndrome (MetS) in childhood-onset systemic lupus erythematosus (cSLE), we performed a cross-sectional study of 76 consecutive cSLE patients and 54 healthy controls, age and sex matched. All individuals were assessed for anthropometric and MetS features according to World Health Organization (WHO), NCEP Adult Treatment Panel III (NCEP-ATP III), and International Diabetes Federation (IDF) criteria. The cSLE patients were further assessed for clinical and laboratory manifestations, disease activity (Systemic Lupus Erythematosus Disease Activity Index), cumulative damage (Systemic Lupus International Collaborating Clinics (SLICC)), and current and cumulative drug exposures. Sixty-nine (90.8%) patients were female with mean age of 16.8 years [standard deviation (SD) ±4.0 years]. Mean disease duration was 4.8 years (SD ± 4.1). Based on the WHO MetS criteria, MetS was observed in two (2.6%) cSLE patients. We observed high prevalence of the MetS in cSLE patients according to NCEP-ATP III MetS criteria (18.4%) (p = 0.002) and according to IDF MetS criteria (17.1%) (p = 0.003). We did not observe MetS in the control group. No difference in cSLE patients <18 and ≥18 years was observed. We observed an association between the presence of MetS and SLICC scores in cSLE <18 years and cumulative corticosteroid dose adjusted by weight in cSLE ≥18 years. This study showed that MetS is frequently observed in cSLE using NCEP-ATP III MetS criteria and IDF MetS criteria. The identification of MetS is important to indicate cardiovascular morbidity and mortality in cSLE.

Drugs in early clinical development for Systemic Lupus Erythematosus.

INTRODUCTION: While immunosuppressive therapy has positively impacted the prognosis of systemic lupus erythematosus (SLE), many patients still do not respond to traditional therapy. Thus, active SLE disease remains a significant problem. Furthermore, conventional immunosuppressive treatments for SLE are associated a high risk of side effects. These issues call for improvement in our current therapeutic armamentarium. AREAS COVERED: In this review, the authors highlight the recent developments in therapies for SLE, and present an overview of drugs which are in early clinical development for SLE. There are many new therapeutic approaches being developed, including those focused on B-cell targets, T-cell downregulation, co-stimulatory blockade, anti-cytokine agents, and kinase inhibition, and Toll-like receptor inhibition. They also discuss peptide therapy as a potential method to re-establish immune tolerance, and some of the challenges ahead in developing and testing novel agents for SLE. EXPERT OPINION: Many novel agents are currently in development for SLE, but this encouraging news is tempered by several disappointments in clinical trials and provides a timely moment to reflect on the future of therapeutic development in SLE. It seems likely that biological heterogeneity between patients is a major contributor to difficulty in drug design in SLE.

Depressive symptoms are associated with tumor necrosis factor alpha in systemic lupus erythematosus.

BACKGROUND: Tumor necrosis factor alpha (TNF-α) is deeply related to pathogenesis of neurodevelopmental disorders, especially depression. The aim of this study was to explore potential relationships between sera TNF-α levels and mood and anxiety disorders in systemic lupus erythematosus (SLE) patients. METHODS: We included 153 consecutive SLE patients (women 148; median age 30; range 10-62) and 40 (women 37; mean age 28.5; range 12-59) age- and sex-matched healthy controls. Mood and anxiety disorders were determined through Beck Depression and Beck Anxiety Inventory. SLE patients were further assessed for clinical and laboratory SLE manifestations. TNF-α levels were measured by enzyme-linked immunosorbent assay using commercial kits. RESULTS: Depressive symptoms were identified in 70 (45.7 %) SLE patients and in 10 (25 %) healthy controls (p < 0.001). Anxiety symptoms were identified in 93 (60.7 %) SLE patients and in 16 controls (40 %) (p < 0.001). Sera TNF-α levels were increased in SLE patients with depressive symptoms (p < 0.001) and with anxiety symptoms (p = 0.014). A direct correlation between the severity of depressive symptoms and sera TNF-α levels (r = 0.22; p = 0.003) was observed. TNF-α levels were significantly increased in patients with active disease (p = 0.012). In addition, we observed a correlation between sera TNF-α levels and disease activity (r = 0.28; p = 0.008). In the multivariate analysis, sera TNF-α levels were independently associated with depressive symptoms (t = 3.28; 95 % CI 1.08-2.2; p = 0.002). CONCLUSIONS: Sera TNF-α levels are increased in SLE patients with mood and anxiety disorders. In SLE, sera TNF-α levels are independently associated with mood disorders. The etiology of mood disorders is still debated in SLE, but our findings suggest the presence of immunological basis for depression in SLE.

Serum interleukin-17 levels are associated with nephritis in childhood-onset systemic lupus erythematosus.

OBJECTIVES: To determine the serum interleukin-17 (IL-17) levels in childhood-onset systemic lupus erythematosus patients and to evaluate the association between IL-17 and clinical manifestations, disease activity, laboratory findings and treatment. METHODS: We included 67 consecutive childhood-onset systemic lupus erythematosus patients [61 women; median age 18 years (range 11-31)], 55 first-degree relatives [50 women; median age 40 years (range 29-52)] and 47 age- and sex-matched healthy controls [42 women; median age 19 years (range 6-30)]. The childhood-onset systemic lupus erythematosus patients were assessed for clinical and laboratory systemic lupus erythematosus manifestations, disease activity [Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)], cumulative damage [Systemic Lupus International Collaborating Clinics/American College of Rheumatology (ACR) Damage Index] and current drug use. Serum IL-17 levels were measured by an enzyme-linked immunosorbent assay using commercial kits. RESULTS: The median serum IL-17 level was 36.3 (range 17.36-105.92) pg/mL in childhood-onset systemic lupus erythematosus patients and 29.47 (15.16-62.17) pg/mL in healthy controls (p=0.009). We observed an association between serum IL-17 levels and active nephritis (p=0.01) and migraines (p=0.03). Serum IL-17 levels were not associated with disease activity (p=0.32), cumulative damage (p=0.34), or medication use (p=0.63). CONCLUSION: IL-17 is increased in childhood-onset systemic lupus erythematosus and may play a role in the pathogenesis of neuropsychiatric and renal manifestations. Longitudinal studies are necessary to determine the role of IL-17 in childhood-onset systemic lupus erythematosus.

Serum interleukin-17 levels are associated with nephritis in childhood-onset systemic lupus erythematosus

OBJECTIVES: To determine the serum interleukin-17 (IL-17) levels in childhood-onset systemic lupus erythematosus patients and to evaluate the association between IL-17 and clinical manifestations, disease activity, laboratory findings and treatment. METHODS: We included 67 consecutive childhood-onset systemic lupus erythematosus patients [61 women; median age 18 years (range 11-31)], 55 first-degree relatives [50 women; median age 40 years (range 29-52)] and 47 age- and sex-matched healthy controls [42 women; median age 19 years (range 6-30)]. The childhood-onset systemic lupus erythematosus patients were assessed for clinical and laboratory systemic lupus erythematosus manifestations, disease activity [Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)], cumulative damage [Systemic Lupus International Collaborating Clinics/American College of Rheumatology (ACR) Damage Index] and current drug use. Serum IL-17 levels were measured by an enzyme-linked immunosorbent assay using commercial kits. RESULTS: The median serum IL-17 level was 36.3 (range 17.36-105.92) pg/mL in childhood-onset systemic lupus erythematosus patients and 29.47 (15.16-62.17) pg/mL in healthy controls (p=0.009). We observed an association between serum IL-17 levels and active nephritis (p=0.01) and migraines (p=0.03). Serum IL-17 levels were not associated with disease activity (p=0.32), cumulative damage (p=0.34), or medication use (p=0.63). CONCLUSION: IL-17 is increased in childhood-onset systemic lupus erythematosus and may play a role in the pathogenesis of neuropsychiatric and renal manifestations. Longitudinal studies are necessary to determine the role of IL-17 in childhood-onset systemic lupus erythematosus. .

Obesity and cytokines in childhood-onset systemic lupus erythematosus.

BACKGROUND: In systemic lupus erythematosus (SLE), atherosclerosis is attributed to traditional and lupus related risk factors, including metabolic syndrome (MetS), obesity, and inflammation. Objective. To evaluate the association between obesity, measures of body fat content, serum tumor necrosis factor alpha (TNF-α), and interleukin (IL)-6 and -10 levels in childhood-onset SLE (cSLE). METHODS: We screened consecutive cSLE patients followed up in the Pediatric Rheumatology Outpatient Clinic of the State University of Campinas. cSLE patients were assessed for disease and damage. Obesity was definite as body mass index (BMI) ≥30 kg/m(2). Serum TNF-α, IL-6, and IL-10 levels were measured by ELISA. Dual-energy X-ray absorptiometry was used to determine total fat mass, lean mass, and percent of body fat. RESULTS: We included 52 cSLE patients and 52 controls. cSLE patients had higher serum TNF-α (P = 0.004), IL-6 (P = 0.002), and IL-10 (P < 0.001) levels compared to controls. We observed higher serum TNF-α (P = 0.036) levels in cSLE patients with obesity. An association between serum TNF-α levels and body fat percent (P = 0.046) and total fat mass on trunk region (P = 0.035) was observed. CONCLUSION: Serum TNF-α levels were associated with obesity and body fat content in cSLE. Our finding suggests that obesity may contribute to the increase of serum TNF-α levels in cSLE.

Risk factors in cardiovascular disease in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic and multisystemic autoimmune disorder which predominantly affecting women. The most common cause of death in SLE patients affected by disease for more than 5 years is cardiovascular disease (CVD). Epidemiological observations suggest that, together with classical conventional risk factors, other mechanisms (non-conventional/disease-specific factors) promote accelerated atherosclerosis in inflammatory diseases like SLE. Traditional CVD risk factors included age, hypertension, diabetes mellitus, dyslipidemia, previous vascular event defined as previous history of cerebrovascular accidents or ischemic heart disease, menopause and smoking. The nontraditional factors presents in SLE are disease-specific like renal disease manifestation as Lupus nephritis (LN), presence of pro-inflammatory cytokines, some of inflammatory mediators, antiphospholipid antibodies, anti-oxLDL antibodies, corticosteroid uses and cumulative dose of glucocorticoids. We will review traditional and non-traditional risk factors associated with CVD in SLE patients.

Síndrome metabólica e composição corporal nos pacientes com lúpus eritematoso sistêmico juvenil / Metabolic syndrome and body composition in patients with childhood on set systemic lupus erythematosus

Lupus Eritematoso Sistêmico (LES) e uma doença autoimune, crônica e mutissistemica, caracterizada por períodos de atividade e remissão. Anormalidades como leucopenia, anemia hemolítica, presença de auto-anticorpos como anti-DNA de fita dupla (anti-dsDNA), anti-Smith (anti-Sm) e fator antinuclear (FAN) podem ser encontradas. Quando diagnosticado ate os 16 anos de idade e denominado LESj. Devido ao elevado acometimeto cardíaco nesses pacientes e muito importante avaliar os fatores de risco para o desenvolvimento de doenças coronarianas. O presente estudo, de característica transversal, teve como objetivo avaliar a presença de SM nos pacientes com LESj e comparar com controles sem histórico de doença autoimune e cardiovasculares e avaliar a composição corporal e observar a associação com a atividade e dano da doença, uso de corticosteróides e TNF-?. Foram selecionados pacientes consecutivos com LESj acompanhados na Unidade de Reumatologia Pediátrica da UNICAMP entre 2010/2012. Manifestações clinicas, laboratoriais e medicação em uso foram avaliadas. A atividade da doença [SLE Disease Activity Index (SLEDAI)], dano cumulativo [Lupus International Collaborating Clinics (SLICC)] foi determinado para cada paciente no dia da coleta de sangue. A SM foi avaliada através do critério da IDF - International diabetes federation. A dosagem da citocina foi realizada por ELISA (Enzyme Linked Immuno Sorbent Assay). Observamos uma prevalência de SM de aproximadamente 20% dos pacientes incluídos. Observamos um numero similar de pacientes com LES <18 anos com síndrome metabólica quando comparada com ? 18 anos de idade (p = 0,202).

Systemic lupus erythematosus (SLE) is a chronic, multisystemic, relapsing and remitting autoimmune disease. Abnormalities such as leukopenia, hemolytic anemia, presence of autoantibodies such as anti-double-stranded DNA (anti-dsDNA), anti-Smith (anti-Sm) and antinuclear antibodies (ANA) can be found. When the diagnosis was made until 16 years old the patients was called childhood-onset SLE. Because of the greatest rate of cardiac involvement of these patients is very important to evaluate the risk factors to coronary diseases development The present cross-sectional study aimed to evaluate the presence of MetS in SLE patients and to compare with controls without autoimmune disease history and to evaluate the body composition and observe its association with the activity disease, laboratory data and corticosteroid treatment and TNF-?. We selected consecutive pediatric SLE patients followed at the Pediatric Rheumatology Unit of UNICAMP between 2010/2012. Clinical, laboratory, disease activity [SLE Disease Activity Index (SLEDAI)], cumulative damage [Systemic Lupus International Collaborating Clinics / American College of Rheumatology Damage Index (SDI)] and current drug exposure were evaluated. The MetS was evaluated by IDF - International diabetes federation criteria. The measurement of cytokines was performed by ELISA (Enzyme Linked Immuno Sorbent Assay). The prevalence of MetS in approximately 20% of patients included. We observed a similar number of SLE patients <18 years with MetS compared with ? 18 years of age (p = 0.202). We found that SLE patients <18 years presented with hypertriglyceridemia and patients ? 18 years were more frequently hypercholesterolemia, high LDL-C and hypertriglyceridemia observed correlation of SLEDAI adjusted over time with the definition of the IDF in SLE patients ? 18 years (r = 0.229, p = 0.033). We also observed a higher ratio HC / WC procedures in patients with SLE compared to the control group (p <0.001).

Th1/Th2 cytokine profile in childhood-onset systemic lupus erythematosus.

OBJECTIVE: To determine the serum levels of Th1 (IL-12, IFN-γ,TNF-α) and Th2 (IL-5, IL-6 and IL-10) cytokines in childhood-onset SLE, first-degree relatives and healthy controls. To elucidate their association with disease activity, laboratory and treatment features. METHODS: We included 60 consecutive childhood-onset SLE patients [median age 18 years (range 10-37)], 64 first-degree relatives [median 40 (range 28-52)] and 57 healthy [median age 19 years (range 6-30 years)] controls. Controls were age and sex-matched to SLE patients. SLE patients were assessed for clinical and laboratory SLE manifestations, disease activity (SLEDAI), damage (SDI) and current drug exposures. Mood and anxiety disorders were determined through Becks Depression (BDI) and Anxiety Inventory (BAI). Th1 (IL-12, IFN-γ,TNF-α) and Th2 (IL-5, IL-6 and IL-10) cytokines levels were measured by ELISA and compared by non-parametric tests. RESULTS: Serum TNF-α (p=0.004), IL-6 (p=0.007) and IL-10 (p=0.03) levels were increased in childhood-onset SLE patients when compared to first-degree relatives and healthy controls. TNF-α levels were significantly increased in patients with active disease (p=0.014) and correlated directly with SLEDAI scores (r=0.39; p=0.002). IL-12 (p=0.042) and TNF-α (p=0.009) levels were significantly increased in patients with nephritis and TNF-α in patients with depression (p=0.001). No association between cytokine levels and SDI scores or medication was observed. CONCLUSION: Th1 cytokines may play a role in the pathogenesis of neuropsychiatric and renal manifestations in childhood-onset SLE. The correlation with SLEDAI suggests that TNF-α may be a useful biomarker for disease activity in childhood-onset SLE, however longitudinal studies are necessary to determine if increase of this cytokine may predict flares in childhood-onset SLE.

Clinical and serological manifestations associated with interferon-α levels in childhood-onset systemic lupus erythematosus.

OBJECTIVE: To determine the serum levels of interferon alpha in childhood-onset systemic lupus erythematosus patients, their first-degree relatives and healthy controls and to evaluate the associations between serum interferon alpha and disease activity, laboratory findings and treatment features. METHODS: We screened consecutive childhood-onset systemic lupus erythematosus patients in a longitudinal cohort at the pediatric rheumatology unit of the State University of Campinas between 2009 and 2010. All patients demonstrated disease onset before the age of 16. Disease status was assessed according to the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). Interferon alpha levels were measured using an enzyme-linked immunoabsorbent assay. RESULTS: We included 57 childhood-onset systemic lupus erythematosus patients (mean age 17.33 ± 4.50), 64 first-degree relatives (mean age 39.95 ± 5.66), and 57 healthy (mean age 19.30 ± 4.97) controls. Serum interferon alpha levels were significantly increased in childhood-onset systemic lupus erythematosus patients compared to their first-degree relatives and healthy controls. Interferon alpha levels were significantly increased in patients with positive dsDNA antibodies, patients with cutaneous vasculitis, patients with new malar rash and patients who were not receiving medication. Interferon alpha levels correlated with C3 levels and systemic lupus erythematosus Disease Activity Index scores. In addition, we observed an inverse correlation between patient age and interferon alpha levels. CONCLUSION: Interferon alpha may play a role in the pathogenesis of childhood-onset systemic lupus erythematosus, especially in cutaneous manifestations and dsDNA antibody formation. The observation that interferon alpha levels are increased in patients who are not taking medication should be investigated in longitudinal studies to determine whether elevated interferon alpha levels may predict systemic lupus erythematosus flares.

Clinical and serological manifestations associated with interferon-α levels in childhood-onset systemic lupus erythematosus

OBJECTIVE: To determine the serum levels of interferon alpha in childhood-onset systemic lupus erythematosus patients, their first-degree relatives and healthy controls and to evaluate the associations between serum interferon alpha and disease activity, laboratory findings and treatment features. METHODS: We screened consecutive childhood-onset systemic lupus erythematosus patients in a longitudinal cohort at the pediatric rheumatology unit of the State University of Campinas between 2009 and 2010. All patients demonstrated disease onset before the age of 16. Disease status was assessed according to the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). Interferon alpha levels were measured using an enzyme-linked immunoabsorbent assay. RESULTS: We included 57 childhood-onset systemic lupus erythematosus patients (mean age 17.33±4.50), 64 firstdegree relatives (mean age 39.95±5.66), and 57 healthy (mean age 19.30±4.97) controls. Serum interferon alpha levels were significantly increased in childhood-onset systemic lupus erythematosus patients compared to their firstdegree relatives and healthy controls. Interferon alpha levels were significantly increased in patients with positive dsDNA antibodies, patients with cutaneous vasculitis, patients with new malar rash and patients who were not receiving medication. Interferon alpha levels correlated with C3 levels and systemic lupus erythematosus Disease Activity Index scores. In addition, we observed an inverse correlation between patient age and interferon alpha levels. CONCLUSION: Interferon alpha may play a role in the pathogenesis of childhood-onset systemic lupus erythematosus, especially in cutaneous manifestations and dsDNA antibody formation. The observation that interferon alpha levels are increased in patients who are not taking medication should be investigated in longitudinal studies to determine whether elevated interferon alpha levels may predict systemic lupus erythematosus flares.

[Aspects of atherosclerosis and metabolic syndrome in lupus erythematosus]. / Aspectos da aterosclerose e da síndrome metabólica no lúpus eritematoso sistêmico.

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease affecting mainly young women. In last decades premature atherosclerosis has been identified as an important cause of mortality due to SLE related risk factors (inflammation and treatment) and metabolic syndrome (MS). MS is a group of risk factors, originating from an abnormal metabolism, with an increased risk for developing atherosclerotic cardiovascular disease. The prevalence of MS varies from 5,5-55,4% in the general population and has been observed up to 40% in SLE, associated with advanced age, low socioeconomic status, lack of exercise, use of high doses of prednisone and disease activity. Treatment should include identification and modification of these risk factors.