Bobek Dubravka, Grčević Danka, Kovačić Nataša, Lukić Ivan Krešimir, Jelušić Marija
Department of Pediatrics, Division of Pediatric Rheumatology and Immunology, University Hospital Centre Zagreb, University of Zagreb School of Medicine, Kišpatićeva 12, 10000 Zagreb, Croatia.
Department of Physiology and Immunology, University of Zagreb School of Medicine, Zagreb, Croatia.
Pediatr Rheumatol Online J. 2014 Dec 3;12:50. doi: 10.1186/1546-0096-12-50. eCollection 2014.
The involvement of high mobility group box-1 (HMGB1) in various inflammatory and autoimmune diseases has been documented but clinical trials on the contribution of this pro-inflammatory alarmin in children with juvenile idiopathic arthritis (JIA) and systemic lupus erythematosus (SLE) are basically absent. To address the presence of HMGB1 and a soluble receptor for advanced glycation end products (sRAGE) in different subtypes of JIA and additionally in children with SLE, we enrolled a consecutive sample of children harvested peripheral blood as well as synovial fluids (SF) at diagnosis and correlated it with ordinary acute-phase reactants and clinical markers.
Serum and synovial fluids levels of HMGB1 and sRAGE in total of 144 children (97 with JIA, 19 with SLE and 27 healthy controls) were determined by ELISA.
The children with JIA and those with SLE were characterised by significantly higher serum levels of HMGB1 and significantly lower sRAGE levels compared to the healthy controls. A positive correlation between serum HMGB1 and ESR, CRP, α2 globulin was found while serum sRAGE levels were inversely correlated with the same inflammatory markers in children with JIA. Additionally, high level of serum HMGB1 was related to hepatosplenomegaly or serositis in systemic onset JIA.
The inverse relationship of the HMGB1 and its soluble receptor RAGE in the blood and SF indicates that inflammation triggered by alarmins may play a role in pathogenesis of JIA as well as SLE. HMGB1 may serve as an inflammatory marker and a potential target of biological therapy in these patients. Further studies need to show whether the determination of HMGB1 levels in patients with JIA can be a useful guideline for detecting disease activity.
高迁移率族蛋白B1(HMGB1)参与多种炎症和自身免疫性疾病已得到证实,但关于这种促炎警报素在幼年特发性关节炎(JIA)和系统性红斑狼疮(SLE)患儿中的作用的临床试验基本缺失。为了研究HMGB1和晚期糖基化终产物可溶性受体(sRAGE)在不同亚型JIA以及SLE患儿中的存在情况,我们纳入了一系列连续样本,这些患儿在诊断时采集了外周血和滑膜液(SF),并将其与普通急性期反应物和临床指标进行关联分析。
采用酶联免疫吸附测定法(ELISA)测定了总共144名儿童(97名JIA患儿、19名SLE患儿和27名健康对照)血清和滑膜液中HMGB1和sRAGE的水平。
与健康对照相比,JIA患儿和SLE患儿的血清HMGB1水平显著升高,sRAGE水平显著降低。在JIA患儿中,血清HMGB1与血沉(ESR)、C反应蛋白(CRP)、α2球蛋白呈正相关,而血清sRAGE水平与相同的炎症标志物呈负相关。此外,血清HMGB1水平升高与全身型JIA的肝脾肿大或浆膜炎有关。
血液和SF中HMGB1及其可溶性受体RAGE的反向关系表明,警报素引发的炎症可能在JIA和SLE的发病机制中起作用。HMGB1可能作为这些患者的炎症标志物和生物治疗的潜在靶点。进一步的研究需要表明,测定JIA患者的HMGB1水平是否可以作为检测疾病活动的有用指导。