巨噬细胞凋亡抑制剂作为日本IgA肾病和过敏性紫癜性肾炎儿童疾病活动度的生物标志物
Apoptosis inhibitor of macrophage as a biomarker for disease activity in Japanese children with IgA nephropathy and Henoch-Schönlein purpura nephritis.
作者信息
Irabu Hitoshi, Shimizu Masaki, Kaneko Shuya, Inoue Natsumi, Mizuta Mao, Tasaki Yuko, Ohta Kazuhide, Yachie Akihiro, Wada Taizo
机构信息
Department of Pediatrics, School of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan.
Department of Pediatrics, Kanazawa Medical Center, Kanazawa, Japan.
出版信息
Pediatr Res. 2021 Feb;89(3):667-672. doi: 10.1038/s41390-020-0951-1. Epub 2020 May 14.
BACKGROUND
To evaluate the apoptosis inhibitor of macrophage (AIM) deposition patterns on the kidneys of children with IgA nephropathy (IgAN) and Henoch-Schönlein purpura nephritis (HSPN) and to investigate the clinical usefulness of serum and/or urinary AIM levels as biomarkers for the disease activity.
METHODS
Immunohistochemical study was performed in the kidneys of 37 patients with IgAN and 10 patients with HSPN. Serum and urinary AIM levels in the patients and 20 healthy controls (HCs) were quantified by enzyme-linked immunosorbent assay. The results were compared with clinical features.
RESULTS
In patients with IgAN and HSPN, AIM expression was observed in various areas, including the glomerular mesangial and capillary areas, the proximal and distal tubular epithelial cells, and on infiltrating macrophages in the glomeruli and interstitial areas. Serum and urinary AIM levels were significantly elevated in these patients compared with the HCs. Urinary AIM levels were positively correlated with the histological severity and degree of proteinuria and hematuria as well as urinary β2 microglobulin and urinary N-acetyl-β-D-glucosaminidase levels.
CONCLUSIONS
AIM plays an important role in the pathogenesis of IgAN and HSPN. Urinary AIM levels can potentially reflect active renal inflammation in these diseases and may represent a useful biomarker for disease activity.
IMPACT
Urinary AIM levels may represent a useful biomarker for disease activity of IgAN and HSPN. AIM expression was observed in the glomeruli, tubular epithelial cells, and infiltrating macrophages in glomeruli and interstitial area. U-AIM/Cr were significantly correlated not only with proteinuria, hematuria, and u-β2MG and u-NAG levels but also with the activity index of histological findings in kidney biopsy specimens. Our results can emphasize the important role of AIM in the pathogenesis of IgAN and HSPN.
背景
评估巨噬细胞凋亡抑制剂（AIM）在IgA肾病（IgAN）和过敏性紫癜性肾炎（HSPN）患儿肾脏中的沉积模式，并研究血清和/或尿AIM水平作为疾病活动生物标志物的临床实用性。
方法
对37例IgAN患者和10例HSPN患者的肾脏进行免疫组织化学研究。采用酶联免疫吸附测定法对患者和20名健康对照者（HCs）的血清和尿AIM水平进行定量。将结果与临床特征进行比较。
结果
在IgAN和HSPN患者中，AIM表达见于多个区域，包括肾小球系膜和毛细血管区域、近端和远端肾小管上皮细胞，以及肾小球和间质区域的浸润巨噬细胞。与HCs相比，这些患者的血清和尿AIM水平显著升高。尿AIM水平与组织学严重程度、蛋白尿和血尿程度以及尿β2微球蛋白和尿N-乙酰-β-D-氨基葡萄糖苷酶水平呈正相关。
结论
AIM在IgAN和HSPN的发病机制中起重要作用。尿AIM水平可能反映这些疾病中的活动性肾炎症，可能代表疾病活动的有用生物标志物。
影响
尿AIM水平可能是IgAN和HSPN疾病活动的有用生物标志物。在肾小球、肾小管上皮细胞以及肾小球和间质区域的浸润巨噬细胞中观察到AIM表达。尿AIM/肌酐不仅与蛋白尿、血尿、尿β2微球蛋白和尿N-乙酰-β-D-氨基葡萄糖苷酶水平显著相关，而且与肾活检标本的组织学结果活动指数显著相关。我们的结果可以强调AIM在IgAN和HSPN发病机制中的重要作用。
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