Pillebout Evangeline, Jamin Agnès, Ayari Hamza, Housset Pierre, Pierre Melissa, Sauvaget Virginia, Viglietti Denis, Deschenes Georges, Monteiro Renato C, Berthelot Laureline
INSERM 1149, Center of Research on Inflammation (CRI), Paris, France.
Inflamex, Laboratory of Excellence, Bichat Medical Faculty, Paris, France.
PLoS One. 2017 Nov 30;12(11):e0188718. doi: 10.1371/journal.pone.0188718. eCollection 2017.
Henoch-Schönlein purpura is a systemic vasculitis characterized by IgA deposits, which target the skin, joints, and kidneys, among other organs. In children, prognosis is often good but little is known about biomarkers of pediatric nephritis. We hypothesized that biological markers, including cytokines, immunoglobulins, IgA-immune complexes, IgA glycosylation and neutrophil gelatinase-associated lipocalin (NGAL), may discriminate IgA vasculitis (IgAV) pediatric patients with renal involvement from those without renal involvement. Fifty children at the time of IgAV rash between 2010 and 2015 were prospectively enrolled and compared to 21 controls. All patients were assessed for clinical and biological parameters at the time of diagnosis, including the levels of cytokines, immunoglobulins, immune complexes, IgA glycosylation and NGAL in serum and urine. Among IgAV patients, 33 patients exhibited nephritis (IgAV-N) and 17 children were without nephritis (IgAV-woN). The serum level of galactose-deficient (Gd)-IgA1 (p<0.01) and the urinary concentrations of IgA, IgG, IgM, IL-6, IL-8, IL-10, IgA-IgG complexes and IgA-sCD89 complexes (p<0.001 for all) were higher in the IgAV-N patients than in the IgAV-woN patients. Among those markers, urinary IgA and IgM had the highest AUC (0.86 and 0.87 respectively, p<0.0001). This prospective cohort study furthers our understanding of the pathophysiology of IgAV. We identified biomarkers that are able to distinguish patients initially with or without nephritis. To conclude, serum Gd-IgA1 and urinary IgA, IgG, IgM, IL-6, IL-8, IL-10, and IgA-IgG and IgA-sCD89 complexes could identify IgAV pediatric patients with renal involvement at the time of diagnosis.
过敏性紫癜是一种系统性血管炎,其特征为IgA沉积,可累及皮肤、关节和肾脏等多个器官。在儿童中,预后通常良好,但关于小儿肾炎的生物标志物知之甚少。我们推测,包括细胞因子、免疫球蛋白、IgA免疫复合物、IgA糖基化和中性粒细胞明胶酶相关脂质运载蛋白(NGAL)在内的生物标志物,可能有助于区分有肾脏受累的IgA血管炎(IgAV)小儿患者和无肾脏受累的患者。2010年至2015年间,前瞻性纳入了50例出现IgAV皮疹的儿童,并与21例对照进行比较。在诊断时对所有患者的临床和生物学参数进行评估,包括血清和尿液中的细胞因子、免疫球蛋白、免疫复合物、IgA糖基化和NGAL水平。在IgAV患者中,33例出现肾炎(IgAV-N),17例儿童无肾炎(IgAV-woN)。IgAV-N患者的血清半乳糖缺乏(Gd)-IgA1水平(p<0.01)以及尿液中IgA、IgG、IgM、IL-6、IL-8、IL-10、IgA-IgG复合物和IgA-sCD89复合物的浓度(所有p<0.001)均高于IgAV-woN患者。在这些标志物中,尿液IgA和IgM的曲线下面积(AUC)最高(分别为0.86和0.87,p<0.0001)。这项前瞻性队列研究加深了我们对IgAV病理生理学的理解。我们确定了能够区分最初有无肾炎的患者的生物标志物。总之,血清Gd-IgA1以及尿液中的IgA、IgG、IgM、IL-6、IL-8、IL-10、IgA-IgG和IgA-sCD89复合物可在诊断时识别有肾脏受累的IgAV小儿患者。