Progressive IgA Nephropathy Is Associated With Low Circulating Mannan-Binding Lectin-Associated Serine Protease-3 (MASP-3) and Increased Glomerular Factor H-Related Protein-5 (FHR5) Deposition.
Progressive IgA Nephropathy Is Associated With Low Circulating Mannan-Binding Lectin-Associated Serine Protease-3 (MASP-3) and Increased Glomerular Factor H-Related Protein-5 (FHR5) Deposition.
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DOI：
10.1016/j.ekir.2017.11.015
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发表时间：
2018-03
影响因子：
6
通讯作者：
Pickering MC
中科院分区：
文献类型：
--
作者：
Medjeral-Thomas NR;Troldborg A;Constantinou N;Lomax-Browne HJ;Hansen AG;Willicombe M;Pusey CD;Cook HT;Thiel S;Pickering MC
伊加肾病（IgAN）的特征在于半乳糖缺陷型IgA 1和补体蛋白的肾小球沉积并导致肾损害。通过旁路和凝集素激活途径的补体沉积与肾损伤相关。为了阐明凝集素途径对IgAN的贡献，我们测量了IgAN患者的11种血浆凝集素途径组分。与健康对照相比，IgAN患者中M-纤维胶凝蛋白、L-纤维胶凝蛋白、甘露聚糖结合凝集素（MBL）相关丝氨酸蛋白酶（MASP）-1和MBL相关蛋白（MAp）19增加，而血浆MASP-3水平降低。进行性疾病与低血浆MASP-3水平和C3 b/iC 3b/C3 c、C3 d、C4d、C5 b-9和因子H相关蛋白5（FHR 5）的肾小球染色增加相关。肾小球FHR 5沉积与肾小球C3 b/iC 3b/C3 c、C3 d和C5 b-9沉积呈正相关，但与肾小球C4d无关。这些观察结果，连同肾小球H因子（fH）沉积在进行性疾病中减少的发现，与FHR 5在IgAN肾损伤中fH失调的作用一致。我们的数据表明，循环MASP-3水平可用作IgAN中疾病严重程度的生物标志物，并且FHR 5的肾小球染色既可指示替代补体途径活化，又可作为疾病严重程度的组织标志物。
IgA nephropathy (IgAN) is characterized by glomerular deposition of galactose-deficient IgA1 and complement proteins and leads to renal impairment. Complement deposition through the alternative and lectin activation pathways is associated with renal injury. To elucidate the contribution of the lectin pathway to IgAN, we measured the 11 plasma lectin pathway components in a well-characterized cohort of patients with IgAN. M-ficolin, L-ficolin, mannan-binding lectin (MBL)–associated serine protease (MASP)-1 and MBL-associated protein (MAp) 19 were increased, whereas plasma MASP-3 levels were decreased in patients with IgAN compared with healthy controls. Progressive disease was associated with low plasma MASP-3 levels and increased glomerular staining for C3b/iC3b/C3c, C3d, C4d, C5b-9, and factor H–related protein 5 (FHR5). Glomerular FHR5 deposition positively correlated with glomerular C3b/iC3b/C3c, C3d, and C5b-9 deposition, but not with glomerular C4d. These observations, together with the finding that glomerular factor H (fH) deposition was reduced in progressive disease, are consistent with a role for fH deregulation by FHR5 in renal injury in IgAN. Our data indicate that circulating MASP-3 levels could be used as a biomarker of disease severity in IgAN and that glomerular staining for FHR5 could both indicate alternative complement pathway activation and be a tissue marker of disease severity.
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影响因子：
4.4
作者：
Iwaki, Daisuke;Kanno, Kazuko;Fujita, Teizo
通讯作者：
Fujita, Teizo
影响因子：
2.7
作者：
Benjamini, Yoav;Krieger, Abba M.;Yekutieli, Daniel
通讯作者：
Yekutieli, Daniel
影响因子：
2.2
作者：
Degn, Soren E.;Jensen, Lisbeth;Thiel, Steffen
通讯作者：
Thiel, Steffen
影响因子：
13.6
作者：
Berthoux, Francois;Suzuki, Hitoshi;Novak, Jan
通讯作者：
Novak, Jan
影响因子：
39.2
作者：
Levey AS;Stevens LA;Schmid CH;Zhang YL;Castro AF 3rd;Feldman HI;Kusek JW;Eggers P;Van Lente F;Greene T;Coresh J;CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration)
通讯作者：
CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration)