Marro Julien, Chetwynd Andrew J, Wright Rachael D, Dliso Silothabo, Oni Louise
Department of Women's and Children's Health, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L12 2AP, UK.
NIHR Alder Hey Clinical Research Facility, Clinical Research Division, Alder Hey Children's NHS Foundation Trust, Liverpool L14 5AB, UK.
Children (Basel). 2022 Apr 27;9(5):622. doi: 10.3390/children9050622.
Chronic kidney disease is a recognised complication of immunoglobulin A vasculitis, (IgAV; formerly Henoch-Schonlein purpura-HSP). The pathophysiology of IgAV and why some patients develop significant renal involvement remains largely unknown. Identifying urinary inflammatory markers could direct targets for earlier intervention. The aim of this cross-sectional exploratory study was to perform a large protein array analysis to identify urinary markers to provide insight into the mechanisms of kidney inflammation in children with established IgAV nephritis (IgAVN). Determination of the relative levels of 124 key proteins was performed using commercially available proteome profiler array kits. Twelve children were recruited: IgAVN, = 4; IgAV without nephritis (IgAVwoN), = 4; healthy controls (HCs), = 4. The urinary concentrations of twenty proteins were significantly different in IgAVN compared to IgAVwoN. The largest fold changes were reported for B-cell activating factor (BAFF), Cripto-1, sex-hormone-binding globulin and angiotensinogen. The urinary levels of complement components C5/C5a and factor D were also significantly elevated in patients with IgAVN. A total of 69 urinary proteins significantly raised levels in comparisons made between IgAVN vs. HCs and nine proteins in IgAVwoN vs. HCs, respectively. This study identified key urinary proteins potentially involved in IgAVN providing new insight into the pathophysiology. Further longitudinal studies with larger cohorts are needed to quantitatively analyse these biomarkers.
慢性肾脏病是免疫球蛋白A血管炎(IgAV;原称过敏性紫癜-HSP)公认的并发症。IgAV的病理生理学以及为何有些患者会出现严重的肾脏受累情况在很大程度上仍不清楚。识别尿液中的炎症标志物可为早期干预指明目标。这项横断面探索性研究的目的是进行大规模蛋白质阵列分析,以识别尿液标志物,从而深入了解已确诊IgA肾病(IgAVN)儿童的肾脏炎症机制。使用市售的蛋白质组分析试剂盒测定124种关键蛋白质的相对水平。招募了12名儿童:IgAVN组4例;无肾炎的IgAV(IgAVwoN)组4例;健康对照组(HCs)4例。与IgAVwoN相比,IgAVN患者尿液中20种蛋白质的浓度有显著差异。B细胞活化因子(BAFF)、Cripto-1、性激素结合球蛋白和血管紧张素原的倍数变化最大。IgAVN患者尿液中补体成分C5/C5a和因子D的水平也显著升高。在IgAVN与HCs的比较中,共有69种尿液蛋白质水平显著升高,在IgAVwoN与HCs的比较中分别有9种蛋白质水平显著升高。本研究确定了可能参与IgAVN的关键尿液蛋白质,为病理生理学提供了新的见解。需要进一步开展更大样本量的纵向研究来对这些生物标志物进行定量分析。