Complement Activation Is Associated With Crescents in IgA Nephropathy.
Complement Activation Is Associated With Crescents in IgA Nephropathy.
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补体激活与 IgA 肾病新月体相关
DOI：
10.3389/fimmu.2021.676919
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发表时间：
2021
影响因子：
7.3
通讯作者：
Zhang H
中科院分区：
文献类型：
--
作者：
Wang Z;Xie X;Li J;Zhang X;He J;Wang M;Lv J;Zhang H
新月体，特别是那些发现的百分比大于50%，往往与伊加肾病（IgAN）的肾脏疾病的快速进展有关。IgAN新月体形成的机制尚不清楚。在这项研究中，我们的目的是评估是否过量的补体激活参与新月体在IgA肾病的形成。100例IgAN患者的新月体的比例不同-24与1%-24%，27与25%-49%，21与50%-74%，12与75%以上，16没有新月体。在活检时测量甘露糖结合凝集素（MBL）、Bb、C4d、C3 a、C5 a和可溶性C5 b-9（sC 5 b-9）的尿浓度。采用受试者工作特征（ROC）曲线评价尿补体激活对肾存活的预测能力。此外，通过免疫组织化学染色历史C4d、C5 b-9和C3 d。新月体形成超过50%的IgAN患者的补体激活水平高于其他患者（尿C3 a/肌酐（C3 a/Cr）：6.7295 ng/mg，四分位距（IQR）1.4652-62.1086 ng/mg vs. 0.1055 ng/mg，IQR 0-1.4089 ng/mg;尿C5 a/Cr：15.6202 ng/mg，4.3127-66.7347 ng/mg vs. 0.3280 ng/mg，IQR 0.0859-2.4439 ng/mg;尿sC5b-9/Cr：98.6357 ng/mg，8.8058- 1，087.4578 ng/mg对比1.4262 ng/mg，0.0916-11.0858 ng/mg，所有p值<0.001）。代表凝集素补体途径的尿MBL和C4d水平与新月体比例呈线性相关（r分别为0.457和0.562，均P值<0.001）。与单独使用新月体相比，联合使用尿补体产品可将预测能力从0.904提高到0.944（p = 0.062），具有临界显著性。肾小球C4d沉积率随新月体比例的增加而升高。过度的补体激活可能参与IgAN患者新月体的形成，尤其是弥漫性新月体的形成。尿C4d与新月体比例相关，是新月体IgAN疾病监测的潜在生物标志物。
Crescents, especially those found at a percentage greater than 50%, are often associated with rapid progression of kidney disease in IgA nephropathy (IgAN). The mechanism of crescents forming in IgAN is still unclear. In this study, we aimed to evaluate whether excess complement activation participates in the formation of crescents in IgAN. One hundred IgAN patients with various proportions of crescents—24 with 1%–24%, 27 with 25%–49%, 21 with 50%–74% 12 with more than 75%, and 16 without crescents—were included. Urinary concentrations of mannose-binding lectin (MBL), Bb, C4d, C3a, C5a, and soluble C5b-9 (sC5b-9) were measured at the time of biopsy. Receiver operating characteristic (ROC) curves were performed to evaluate predictive ability of renal survival for urine complement activation. In addition, historical C4d, C5b-9, and C3d were stained by immunohistochemistry. IgAN patients with more than 50% crescent formation showed higher complement activation levels than the other patients (urinary C3a/creatinine (C3a/Cr): 6.7295 ng/mg, interquartile range (IQR) 1.4652–62.1086 ng/mg vs. 0.1055 ng/mg, IQR 0–1.4089 ng/mg; urinary C5a/Cr: 15.6202 ng/mg, 4.3127–66.7347 ng/mg vs. 0.3280 ng/mg, IQR 0.0859–2.4439 ng/mg; urinary sC5b-9/Cr: 98.6357 ng/mg, 8.8058–1,087.4578 ng/mg vs. 1.4262 ng/mg, 0.0916–11.0858 ng/mg, all p-values <0.001). The levels of urinary MBL and C4d representing lectin complement pathway showed a linear association with the proportion of crescents (r = 0.457 and 0.562, respectively, both p-values <0.001). Combined urine complement products could increase the predictive ability compared with crescents alone from 0.904 to 0.944 (p = 0.062) with borderline significance. Moreover, the glomerular C4d deposition rate elevated with the increase of proportions of crescents. Excess complement activation may be involved in the formation of crescents, especially diffuse crescent formation, in patients with IgAN. Urinary C4d correlated with the proportion of crescents and was a potential biomarker for disease monitoring in crescentic IgAN.
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