Division of Rheumatology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University and Tygerberg Academic Hospital, Cape Town, South Africa.
Division of Clinical Pharmacology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University and Tygerberg Academic Hospital, Cape Town, South Africa.
Rheumatology (Oxford). 2021 Apr 6;60(4):2010-2021. doi: 10.1093/rheumatology/keaa540.
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.
通过心脏磁共振（CMR）标准识别与系统性红斑狼疮（SLE）心肌损伤（MInj）相关的细胞因子、内皮激活标志物[可溶性血管细胞黏附分子-1（sVCAM-1）]和心肌应变标志物[可溶性 ST2（sST2）]。
对 SLE 患者进行 CMR 检查，确定 MInj 分期（炎症和坏死或纤维化）。采集的数据包括：临床评估、实验室和血清学分析、细胞因子（IL-1β、IL-1Ra、IL-2、IL-6、IL-10、IL-17、IL-18、TNF-α）、sVCAM-1 和 sST2 水平。比较细胞因子与 SLE 特征和 CMR MInj 证据。通过回归分析确定 CMR MInj 的预测因子。
共纳入 41 例疾病活动度高的患者（SLEDAI-2K：13；IQR：3-17）。SLE 特征包括：狼疮肾炎（n=12）、神经狼疮（n=6）和临床狼疮性心肌炎（LM）（n=6）。19 例患者 CMR 有 MInj 证据。SLEDAI-2K≥12 的患者 sVCAM-1（P=0.010）和 sST2（P=0.032）水平更高。神经狼疮与更高的 IL-1Ra（P=0.038）相关，狼疮肾炎与更低的 IL-1Ra（P=0.025）和 sVCAM-1（P=0.036）水平相关。与无 CMR MInj 的患者相比，CMR MInj 患者的 IL-1Ra（P=0.012）、IL-17（P=0.045）、IL-18（P=0.003）和 sVCAM-1（P=0.062）水平更高。多变量逻辑回归显示，IL-1Ra 预测 CMR 炎症和纤维化/坏死（P<0.005），而抗 Ro/SSA（优势比（OR）：1.197；P=0.035）和 SLE 损伤指数（OR：4.064；P=0.011）预测纤维化/坏死。
这是对细胞因子与 SLE MInj 之间关联的新描述。MInj 患者的 IL-18 和 IL-1Ra 明显升高。IL-1Ra 独立预测 CMR MInj 的不同分期。探索这些细胞因子在 SLE MInj 发病机制中的作用，可能会促进针对 LM 的靶向治疗。
