459 Systemic lupus erythematosus and severity of illness are associated with t helper 1 and 17 cytokines profiles together with a lowered il-4 production

<h3>Background and aims</h3> To delineate cytokines profiles of systemic lupus erythematosus (SLE), construct prediction models for diagnosis and disease activity using those profiles, and examine how TNFB Ncol polymorphism, body mass index (BMI), vitamin D, and cortisol influence cytokine levels in SLE. <h3>Methods</h3> 200 SLE patients and 196 healthy controls participated in this case-control study. Plasma cytokines levels of TNF-α, IFN-γ, IL-1β, IL-4, IL-6, IL-10, IL-12, IL-17 were measured and cytokines profiles were computed. <h3>Results</h3> 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 pro-inflammatory cytokine profile (TNFα + IL-6 + IL-1β). 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%). 20.9% of the variance in the SLEDAI 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. <h3>Conclusions</h3> SLE is accompanied by Th1, Th17, and Treg profile and lowered IL-4 production. Lowered vitamin D levels and B1/B1 genotype, but not cortisol or BMI, contribute to changes in cytokines profiles. Future treatments should target Th1, Th2 and Th17 profiles rather than inflammatory cytokines.