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

Objective: To determine the serum levels of Th1 (IL-12, IFN-gamma,TNF-alpha) 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 630 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-gamma,TNF-alpha) and Th2 (IL-5, IL-6 and IL-10) cytokines levels were measured by ELISA and compared by non-parametric tests. Results: Serum TNF-alpha (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-alpha 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-alpha (p = 0.009) levels were significantly increased in patients with nephritis and TNF-alpha 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-alpha 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. (C) 2012 Elsevier Ltd. All rights reserved.61378579

Obesity and Cytokines in Childhood-Onset Systemic Lupus Erythematosus

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)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-alpha), 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-alpha, 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-alpha (P = 0.004), IL-6 (P = 0.002), and IL-10 (P < 0.001) levels compared to controls. We observed higher serum TNF-alpha (P = 0.036) levels in cSLE patients with obesity. An association between serum TNF-alpha levels and body fat percent (P = 0.046) and total fat mass on trunk region (P = 0.035) was observed. Conclusion. Serum TNF-alpha levels were associated with obesity and body fat content in cSLE. Our finding suggests that obesity may contribute to the increase of serum TNF-alpha levels in cSLE.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)FAPESP [2008/02917-0, 2010/13637-9, 2011/03788-2]CNPq [300447/2009-4, 471343/2011-0, 302205/2012-8

Prevalence and clinical significance of anti-ribosomal P antibody in childhood-onset systemic lupus erythematosus

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Objective: To investigate the prevalence of the anti-ribosomal P (anti-P) antibodies in childhood-onset systemic lupus erythematosus patients (cSLE), healthy controls and first degree relatives. To elucidate the association between anti-P and disease activity, laboratory and treatment features in cSLE patients. Methods: We included consecutive SLE patients with disease onset before 16 years. Controls were age- and sex-matched. SLE patients were assessed for clinical and laboratory SLE manifestations, disease activity (SLE Disease Activity Index (SLEDAI)), damage (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI)) and current drug exposures. Mood disorders were determined through Becks Depression and Becks Anxiety Inventory. Anti-P measured by enzyme-linked immunosorbent assay. Results: We included 50 consecutive cSLE patients (mean age of 16.82 +/- 3.46 years), 35 first degree relatives (mean age of 38.73 +/- 3.89 years) and 20 health control (mean age of 18.3 +/- 4.97 years). Anti-P was observed in 13 (26%) cSLE patients and in no first-degree relative (p < 0.01) or control (p < 0.01). Anti-P was more frequently observed in patients with anxiety (p < 0.002). No other clinical, laboratory or treatment features, including SLEDAI and SDI scores were associated with the presence of anti-P in cSLE patients. Conclusion: Anti-P is frequently observed in cSLE patients and was associated with the presence of anxiety in this cohort of cSLE. Lupus (2012) 21, 1225-1231.211112251231Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)FAPESP [FAPESP 2008/02917-0, 2009/06049-6, 2009/13046-3]CNPq [300447/2009-4

Olfactory function in systemic lupus erythematosus and systemic sclerosis: a longitudinal study and review of the literature

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. 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. 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. 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 observed17440541