The aims of this study were to delineate cytokine profiles of systemic lupus erythematosus (SLE), construct prediction models for diagnosis and disease activity using those profiles, and to examine the associations between TNFB Ncol polymorphism, body mass index (BMI) and vitamin D levels with cytokine levels. Two hundred SLE patients and 196 healthy controls participated in this case-control study. Plasma cytokines levels of tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-1β, IL- 4, IL-6, IL-10, IL-12 and IL-17 were measured and cytokines profiles were computed. IL-6, IL-12, IL-17, IFN-γ and IL-10 levels were significantly higher in SLE, while IL-4 was lower in SLE. The Th1/Th2 and Th1+Th17/Th2 profiles were significantly higher in SLE than in healthy controls, whereas there were no significant differences in the proinflammatory cytokine profile (TNFα+IL-6+IL-1β). In total, 90.4% of all subjects were correctly classified using Th1+Th17 profile and IL-10 (positively associated) and IL-4 (negatively associated) as predictor variables (sensitivity=66.7% and specificity=96.9%). In all, 20.9% of the variance in the SLE Disease Activity Index was predicted by the Th1+Th17/Th2 ratio, IL-10 and BMI (all positively) and proinflammatory profile (inversely associated). B1/B1 genotype is accompanied by increased IL-17 and Th17/Th2 ratio, while B1/B2 genotype is accompanied by higher IL-4 and IFNγ values. 25-OH vitamin D was inversely associated with IFN-γ levels. SLE is accompanied by Th1, Th17 and Treg profile and lowered IL-4 production. Lowered vitamin D levels and B1/B1 genotype, but not BMI, contribute to changes in cytokines profiles. Future treatments should target Th1, Th2 and Th17 profiles rather than inflammatory cytokines.

Background This study was performed to assess adhesion molecules in systemic lupus erythematosus (SLE). Methods This case-control study examined 126 SLE patients and 48 healthy individuals. Blood levels of six adhesion molecules, cortisol, nuclear autoantibody (ANA) and anti-double stranded DNA (anti-dsDNA) titers were measured, while disease activity was assessed using the SLE Disease Activity Index (SLEDAI) score. Results Platelet endothelial cell adhesion molecule 1 (PECAM-1), vascular cell adhesion molecule 1 (VCAM-1), E-selectin, P-selectin, and plasminogen activator inhibitor type-1 (PAI-1) were significantly higher in SLE patients than in controls. Binary logistic regression analysis showed that PECAM-1 and PAI-1 predicted SLE with a sensitivity of 86.5% and a specificity of 81.3%. ANA titers were significantly and positively associated with PECAM-1, VCAM-1, E-selectin, and PAI-1, whereas there were no associations between anti-dsDNA titers and adhesion molecules. Cortisol was negatively associated with PCAM-1 and ICAM-1. There were significant associations between metabolic syndrome (MetS) and E-selectin and PAI-1. 14.8% of the variance in the SLEDAI score was explained by the regression on PECAM-1 and MetS. Conclusions Our data show that adhesion molecules, especially PECAM-1, are significantly associated with SLE and disease activity, suggesting that they play a role in SLE pathophysiology. While MetS, ANA titers and cortisol levels modulate adhesion molecule levels, these associations do not explain the increased levels of adhesion molecules in SLE. Increased levels of adhesion molecules are new drug targets in SLE.

Background and aims To delineate disorders in adhesion molecules in systemic lupus erythematosus (SLE) and to assess whether cortisol, nuclear autoantibody (ANA) titers and the metabolic syndrome (MetS) are associated with adhesion molecules in SLE. Methods 48 healthy individuals and 171 SLE patients were enrolled. Disease activity was determined by SLEDAI (SLE Disease Activity Index) score. Adhesion molecules and cortisol levels were evaluated. Results Platelet endothelial cell adhesion molecule 1 (PECAM-1), Vascular cell adhesion molecule 1 (VCAM-1), E-selectin, Pselectin and Plasminogen activator inhibitor type-1 (PAI-1) were significantly higher in SLE patients. These significant differences could not be explained by the drug treatment. Mycophenolate treatment significantly decreased intercellular adhesion molecule 1 (ICAM-1) and increased E-selectin levels. Binary logistic regression analysis showed that PECAM-1 and PAI-1 predicted SLE with a sensitivity of 86.5% and a specificity of 81.3%. ANA was significantly and positively associated with PECAM-1, VCAM-1, E-selectin, and PAI-1, whilst cortisol was negatively associated with PCAM-1 and ICAM-1. There were significant associations between MetS and E-selectin and PAI-1. 18.2% of the variance in SLEDAI score was