Serum cytokine levels associated with myocardial injury in systemic lupus erythematosus.

Abstract

To identify cytokines, markers of endothelial activation [soluble vascular cell adhesion molecule-1 (sVCAM-1)] and myocyte strain [soluble ST2 (sST2)] associated with myocardial injury (MInj) in SLE, classified by cardiac magnetic resonance (CMR) criteria. CMR was performed on patients with SLE, identifying stages of MInj (inflammation and necrosis or fibrosis). Data captured included: clinical assessment, laboratory and serological analyses, cytokine (IL-1β, IL-1Ra, IL-2, IL-6, IL-10, IL-17, IL-18, TNF-alpha), sVCAM-1 and sST2 levels. Cytokines were compared with regard to SLE features and evidence of CMR MInj. Predictors of CMR MInj were determined through regression analyses. Forty-one patients with high disease activity (SLEDAI-2K: 13; IQR: 3-17) were included. SLE features included: LN (n = 12), neurolupus (n = 6) and clinical lupus myocarditis (LM) (n = 6). Nineteen patients had CMR evidence of MInj. Patients with a SLEDAI-2K ≥ 12 had higher sVCAM-1 (P = 0.010) and sST2 (P = 0.032) levels. Neurolupus was associated with higher IL-1Ra (P = 0.038) and LN with lower IL-1Ra (P = 0.025) and sVCAM-1 (P = 0.036) levels. Higher IL-1Ra (P = 0.012), IL-17 (P = 0.045), IL-18 (P = 0.003), and sVCAM-1 (P = 0.062) levels were observed in patients with CMR MInj compared with those without. On multivariable logistic regression, IL-1Ra predicted CMR inflammation and fibrosis/necrosis (P < 0.005) while anti-Ro/SSA [odds ratio (OR): 1.197; P = 0.035] and the SLE damage index (OR: 4.064; P = 0.011) predicted fibrosis/necrosis. This is a novel description of associations between cytokines and SLE MInj. IL-18 and IL-1Ra were significantly higher in patients with MInj. IL-1Ra independently predicted different stages of CMR MInj. Exploration of the role of these cytokines in the pathogenesis of SLE MInj may promote targeted therapies for LM.