Circulating complement factor H-related protein 5 levels contribute to development and progression of IgA nephropathy
Circulating complement factor H-related protein 5 levels contribute to development and progression of IgA nephropathy
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循环补体因子 H 相关蛋白 5 水平有助于 IgA 肾病的发生和进展。
DOI：
10.1016/j.kint.2018.02.023
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发表时间：
2018-07-01
影响因子：
19.6
通讯作者：
Zhang, Hong
中科院分区：
文献类型：
--
作者：
Zhu, Li;Guo, Wei-yi;Zhang, Hong
伊加肾病（IgAN）是一种与补体系统激活相关的疾病。但影响IgAN补体激活的因素尚未完全清楚。补体因子H（FH）是补体C3激活的重要负调节因子。补体因子H相关蛋白（FHR）-5与因子H具有高度的序列相似性。然而，与H因子不同的是，与活化的C3结合后，它能够进一步活化。以前，我们报道了CFHR 5基因的罕见变异对IgAN易感性的贡献。在这里，我们比较了1126例IgAN患者的FHR-5循环水平，并定期随访153名无关的健康个体，以探讨FHR-5水平与IgAN发展和进展的关系。IgAN患者的循环FHR-5水平显著高于健康人（中位数4.55 [四分位数范围3.58至5.85] mg/ml vs 3.19 [四分位数范围2.55至3.92] mg/ml）。较高的循环FHR-5水平与较低的估计肾小球滤过率、高血压以及严重的OxfordT和Oxford-C评分相关。高FHR-5水平与估计肾小球滤过率下降30%或终末期肾病的风险独立且显著相关（风险比，自然平方根转换FHR-5的标准差增量为1.226; 95%置信区间：1.106-1.359）。因此，循环FHR-5水平是IgAN进展的独立危险因素。
IgA nephropathy (IgAN) is a disease associated with activation of the complement system. But the factors influencing complement activation in IgAN are not fully understood. Complement factor H (FH) is an essential negative regulator of complement C3 activation. Complement factor H-related protein (FHR)-5 shares high sequence similarity with factor H. However, unlike factor H, on binding to activated C3 it enables further activation to proceed. Previously, we reported the contribution of rare variants of the CFHR5 gene to IgAN susceptibility. Here we compared circulating levels of FHR-5 in 1126 patients with IgAN and regular follow-up with those of 153 unrelated healthy individuals to explore the relationship of FHR-5 levels with IgAN development and progression. Circulating FHR-5 levels were significantly elevated in patients with IgAN compared to healthy individuals (median 4.55 [interquartile range 3.58 to 5.85] mg/ml vs 3.19 [interquartile range 2.55 to 3.92] mg/ml). Higher circulating FHR-5 levels were associated with a lower estimated glomerular filtration rate, hypertension, and severe OxfordT and Oxford-C scores. High FHR-5 levels were independently and significantly associated with a risk of developing either a 30% decline in the estimated glomerular filtration rate or end-stage renal disease (hazard ratio, per standard deviation increment of natural square root transformed FHR-5 of 1.226; 95% confidence interval: 1.106-1.359). Thus, the circulating FHR-5 level is an independent risk factor for IgAN progression.