Altered innate, adaptive, and TNF-superfamily soluble inflammatory mediators mark impending systemic lupus erythematosus disease flare, while regulatory mediators distinguish lack of impending disease flare in African-American lupus patients (CCR5P.201)

Abstract

Abstract SLE is a multifaceted disease characterized by immune dysregulation and varied disease activity. We evaluated changes in plasma soluble mediators (n=52) preceding clinically-defined disease flare, in 13 African American (AA) SLE patients who developed disease flare 6 or 12 weeks after baseline assessment compared to matched SLE patients without impending flare and healthy controls. In addition, mediators within samples preceding SLE disease flare and during a clinically stable period from the same individual were compared in 18 AA SLE patients. Patients with impending flare had significant (q<0.01) alterations in 32 soluble mediators at baseline with significantly higher levels of pro-inflammatory mediators, including innate and adaptive cytokines. Baseline levels of regulatory cytokines, including IL-10 and TGF-β, were higher in non-flare SLE patients, while baseline levels of soluble TNFRI, TNFRII, TRAIL, FasL, and CD40L were significantly greater in pre-flare patients (p<0.05). A normalized and weighted combined soluble mediator score was significantly higher in pre-flare SLE patients versus those with stable disease (p<0.0001). Pro-inflammatory soluble mediators are elevated prior to disease flare, while regulatory mediators are elevated during periods of stable disease. Alterations in the balance between inflammatory and regulatory mediators may help identify AA patients at risk of disease flare and help decipher SLE pathogenic mechanisms.