Li Qianqian, Yuan Xiaohan, Shi Sufang, Liu Lijun, Lv Jicheng, Zhu Li, Zhang Hong
Renal Division, Peking University First Hospital; Institute of Nephrology, Peking University; Key Laboratory of Renal Disease, Ministry of Health of China; Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China; Research Units of Diagnosis and Treatment of lmmune-Mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China.
Clin Kidney J. 2022 Sep 20;16(1):184-191. doi: 10.1093/ckj/sfac214. eCollection 2023 Jan.
Immunoglobulin A nephropathy (IgAN) and IgA vasculitis with nephritis (IgAV-N) are considered related diseases and share some similar clinicopathologic phenotypes. Elevated circulating galactose-deficient IgA1 (Gd-IgA1)-containing immune complexes and mucosal immunity were associated with the pathogenesis of IgAN and IgAV-N. Recently, studies have identified that the zonulin level, as a modulator of intestinal permeability, is significantly elevated in several inflammatory and autoimmune-related diseases. However, whether zonulin also plays a role in IgAN and IgAV-N is not clear.
A total of 73 IgAV-N patients, 68 IgAN patients and 54 healthy controls were assessed for circulating zonulin and Gd-IgA1 levels by enzyme-linked immunosorbent assay. The diagnostic efficiency of the combination of zonulin with Gd-IgA1 was evaluated by the area under the receiver operating characteristic curve (AUC) and integrated discrimination improvement (IDI) analysis.
Compared with healthy controls, we found that both IgAV-N and IgAN patients had elevated zonulin and Gd-IgA1 levels ( < .001). Additionally, patients with IgAV-N presented with even higher circulating zonulin levels than patients with IgAN ( = .020). The addition of zonulin to Gd-IgA1 showed better predictive performance than Gd-IgA1 alone in the diagnosis of both IgAN and IgAV-N, as illustrated by a significantly increased AUC (IgAN: 0.805 versus 0.708, = .0021; IgAV-N: 0.886 versus 0.673, < .001) and significant IDI (IgAN: IDI 0.136, < .001; IgAV-N: IDI 0.281, < .001).
Elevated circulating zonulin levels were detected in both patients with IgAV-N and those with IgAN. Combined detection of circulating zonulin and Gd-IgA1 is recommended as a noninvasive diagnostic biomarker for IgAV-N and IgAN.
免疫球蛋白A肾病（IgAN）和IgA血管炎伴肾炎（IgAV-N）被认为是相关疾病，具有一些相似的临床病理表型。循环中含半乳糖缺陷型IgA1（Gd-IgA1）的免疫复合物水平升高和黏膜免疫与IgAN和IgAV-N的发病机制有关。最近，研究发现，作为肠道通透性调节剂的闭合蛋白水平在几种炎症和自身免疫相关疾病中显著升高。然而，闭合蛋白是否也在IgAN和IgAV-N中起作用尚不清楚。
通过酶联免疫吸附测定法评估了73例IgAV-N患者、68例IgAN患者和54名健康对照者的循环闭合蛋白和Gd-IgA1水平。通过受试者操作特征曲线（AUC）下面积和综合判别改善（IDI）分析评估闭合蛋白与Gd-IgA1联合检测的诊断效率。
与健康对照者相比，我们发现IgAV-N患者和IgAN患者的闭合蛋白和Gd-IgA1水平均升高（P <.001）。此外，IgAV-N患者的循环闭合蛋白水平高于IgAN患者（P =.020）。在IgAN和IgAV-N的诊断中，联合检测闭合蛋白和Gd-IgA1比单独检测Gd-IgA1具有更好的预测性能，AUC显著增加（IgAN：0.805对0.708，P =.0021；IgAV-N：0.886对0.673，P <.OO1）和显著的IDI（IgAN：IDI 0.136，P <.001；IgAV-N：IDI O.281，P <.001）说明了这一点。
在IgAV-N患者和IgAN患者中均检测到循环闭合蛋白水平升高。建议联合检测循环闭合蛋白和Gd-IgA1作为IgAV-N和IgAN的非侵入性诊断生物标志物。
