Li Jingyi, Guo Ling, Shi Sufang, Zhou Xujie, Zhu Li, Liu Lijun, Lv Jicheng, Zhang Hong
Renal Division, Peking University First Hospital, Beijing, China.
Peking University Institute of Nephrology, Beijing China.
Kidney Int Rep. 2022 Apr 4;7(6):1219-1228. doi: 10.1016/j.ekir.2022.03.028. eCollection 2022 Jun.
Arteriolar microangiopathic (MA) lesions are independent risk factors for IgA nephropathy (IgAN) patient prognosis, and the underlying mechanism remains to be elucidated. The complement plays an important role in IgAN and thrombotic microangiopathy; however, its role in MA lesions in IgAN remains unclear.
Immunohistochemistry was performed to detect arteriolar complement deposition. Enzyme-linked immunosorbent assay (ELISA) and whole-exome sequencing were performed to explore possible mechanism.
In this study, we found that patients with IgAN with MA lesions have more complement deposition, especially C4d, on renal arterioles than those in patients with arteriolosclerosis (AS) and patients with no vascular lesions (100% vs. 53% vs 14%, < 0.05). Furthermore, our large prospective cohort demonstrated that patients with IgAN with MA lesions had higher levels of Gd-IgA1 (median: 326.98 U/ml, interquartile range 303.46-370.5 vs. 319.22, 292.01-347.3 vs. 321.95, 291.68-350.68, = 0.014) and C3a (122.57 ± 42.07 vs. 93.79 ± 29.49 vs. 93.51 ± 45.87 ng/ml, = 0.01) than those in patients with AS and those with no vascular lesions. However, serum IgA1 and C3 levels were not significantly different. Finally, through whole-exome sequencing, we found that nearly half of the patients with MA lesions had rare genetic variations in complement-related genes.
Our results indicate that the complement is involved in the development of MA lesions in IgAN, which might be associated with the circulating complex containing Gd-IgA1.
小动脉微血管病变（MA）是IgA肾病（IgAN）患者预后的独立危险因素，其潜在机制仍有待阐明。补体在IgAN和血栓性微血管病中起重要作用；然而，其在IgAN的MA病变中的作用仍不清楚。
采用免疫组织化学检测小动脉补体沉积。采用酶联免疫吸附测定（ELISA）和全外显子组测序探索可能的机制。
在本研究中，我们发现伴有MA病变的IgAN患者肾小动脉上的补体沉积更多，尤其是C4d，比动脉硬化（AS）患者和无血管病变患者更多（100%对53%对14%，<0.05）。此外，我们的大型前瞻性队列研究表明，伴有MA病变的IgAN患者的Gd-IgA1水平更高（中位数：326.98 U/ml，四分位间距303.46-370.5对319.22，292.01-347.3对321.95，291.68-350.68，=0.014）和C3a水平更高（122.57±42.07对93.79±29.49对93.51±45.87 ng/ml，=0.01），高于AS患者和无血管病变患者。然而，血清IgA1和C3水平无显著差异。最后，通过全外显子组测序，我们发现近一半的MA病变患者在补体相关基因中有罕见的基因变异。
我们的结果表明补体参与了IgAN中MA病变的发生发展过程，这可能与含有Gd-IgA1循环复合物有关。
