Circulating complement factor H-related proteins 1 and 5 correlate with disease activity in IgA nephropathy.
Circulating complement factor H-related proteins 1 and 5 correlate with disease activity in IgA nephropathy.
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DOI：
10.1016/j.kint.2017.03.043
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发表时间：
2017-10
影响因子：
19.6
通讯作者：
Pickering MC
中科院分区：
文献类型：
--
作者：
Medjeral-Thomas NR;Lomax-Browne HJ;Beckwith H;Willicombe M;McLean AG;Brookes P;Pusey CD;Falchi M;Cook HT;Pickering MC
IgA肾病(IgAN)是慢性肾脏疾病和终末期肾功能衰竭的常见原因，尤其是在年轻人中。由于临床结果多种多样，很难预测对免疫抑制的反应，我们需要了解为什么并确定哪些IgAN患者会发展为进行性肾损害。影响补体因子H相关蛋白(FHR)-1和FHR-3编码基因的缺失多态与免疫球蛋白肾病的保护作用密切相关。一些FHR蛋白，包括FHR-1和FHR-5，拮抗补体因子H(Fh)的能力，补体因子H(Fh)是补体替代途径的主要负调节因子，抑制表面补体激活，这一过程被称为Fh去调节。从一大群患者中，我们证明了血浆FHR-1和FHR-1/Fh比值在IgAN中升高，并与进展性疾病有关。血浆FHR-1与EGFR呈负相关，但在EGFR正常的IgAN患者中，FHR-1仍处于升高状态。血清FHR5在IgAN组略有升高，但与EGFR无关。FHR5水平和FHR-5/FH比值均与进展性疾病无关。然而，较高的血清FHR-5水平与对免疫抑制缺乏反应、毛细血管内高细胞增多的存在以及疾病严重程度的组织学评分(牛津分类MEST评分)相关。因此，FHR-1和FHR-5在IgAN疾病进展中起一定作用。
IgA nephropathy (IgAN) is a common cause of chronic kidney disease and end-stage renal failure, especially in young people. Due to a wide range of clinical outcomes and difficulty in predicting response to immunosuppression, we need to understand why and identify which patients with IgAN will develop progressive renal impairment. A deletion polymorphism affecting the genes encoding the complement factor H-related protein (FHR)-1 and FHR-3 is robustly associated with protection against IgAN. Some FHR proteins, including FHR-1 and FHR-5, antagonize the ability of complement factor H (fH), the major negative regulator of the complement alternative pathway, to inhibit complement activation on surfaces, a process termed fH deregulation. From a large cohort of patients, we demonstrated that plasma FHR-1 and the FHR-1/fH ratio were elevated in IgAN and associated with progressive disease. Plasma FHR-1 negatively correlated with eGFR but remained elevated in patients with IgAN with normal eGFR. Serum FHR5 was slightly elevated in IgAN but did not correlate with eGFR. Neither FHR5 levels nor the FHR-5/fH ratio was associated with progressive disease. However, higher serum FHR-5 levels were associated with a lack of response to immunosuppression, the presence of endocapillary hypercellularity, and histology scores of disease severity (the Oxford Classification MEST score). Thus, FHR-1 and FHR-5 have a role in IgAN disease progression.
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影响因子：
3.5
作者：
Ansari M;McKeigue PM;Skerka C;Hayward C;Rudan I;Vitart V;Polasek O;Armbrecht AM;Yates JR;Vatavuk Z;Bencic G;Kolcic I;Oostra BA;Van Duijn CM;Campbell S;Stanton CM;Huffman J;Shu X;Khan JC;Shahid H;Harding SP;Bishop PN;Deary IJ;Moore AT;Dhillon B;Rudan P;Zipfel PF;Sim RB;Hastie ND;Campbell H;Wright AF
通讯作者：
Wright AF
影响因子：
19.6
作者：
Magistroni R;D'Agati VD;Appel GB;Kiryluk K
通讯作者：
Kiryluk K
影响因子：
6.1
作者：
Barbour, Thomas D.;Pickering, Matthew C.;Cook, H. Terence
通讯作者：
Cook, H. Terence
影响因子：
3.4
作者：
Chakera, Aron;MacEwen, Clare;Roberts, Ian S. D.
通讯作者：
Roberts, Ian S. D.
影响因子：
19.6
作者：
Cattran, Daniel C.;Coppo, Rosanna;Zhang, Hong
通讯作者：
Zhang, Hong