BackgroundTumor 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.MethodsWe 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.ResultsDepressive 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).ConclusionsSera 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.
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.
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.
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