Renal deposition and clearance of recombinant poly-IgA complexes in a model of IgA nephropathy.
Renal deposition and clearance of recombinant poly-IgA complexes in a model of IgA nephropathy.
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伊加肾病模型中重组多聚IgA复合物的肾沉积和清除
DOI：
10.1002/path.5658
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发表时间：
2021-06
期刊：
影响因子：
--
通讯作者：
Jin J
中科院分区：
文献类型：
--
作者：
Xie X;Liu P;Gao L;Zhang X;Lan P;Bijol V;Lv J;Zhang H;Jin J
伊加肾病（IgAN）是全球最常见的肾小球肾炎类型，其遵循慢性但高度可变的进展过程。伊加免疫复合物是IgAN肾脏沉积物的主要来源。除了存在颗粒状IgA 1沉积在肾小球系膜和系膜细胞增生的共同特点，IgA 1沉积和清除在肾脏的详细过程仍然不清楚。我们试图研究伊加沉积和组织可塑性的动态响应存款，包括其肾内清除。我们遵循合成方法以产生伊加Fc（rIgA）和生物素标签之间的重组融合物，其随后用链霉亲和素（SA）诱导以形成寡聚聚IgA模拟物。将未诱导的rIgA（mono-rIgA）和聚合的SA-rIgA（poly-rIgA）静脉内注射到Wistar大鼠中。血浆伊加水平和肾脏和肝脏组织学检查的时间序列。与mono-rIgA相反，这种合成的poly-rIgA类似物仅在肾小球中形成肾沉积物，并且大部分在3小时内被清除。然而，每天重复注射12天，导致长期和更强的肾小球伊加沉积连同IgG和补体C3，与肾小球系膜细胞增殖，基质扩张，和不同程度的蛋白尿和血尿，表型IgAN。离体，多-rIgA结合培养的系膜细胞，并引起细胞因子的产生，除了激活血浆C3，这是一致的伊加免疫复合物在IgAN发病机制的行动。值得注意的是，肾脏能够逆转所有病理表现，并在停止注射后2周恢复正常的肾小球组织学。合成模型显示了肾脏沉积和清除的复杂平衡之间的动力学，以及肾小球愈合的可塑性。总之，结果揭示了现有沉积物在促进更强和更持久的伊加沉积以引起肾损伤方面的启动效应。
IgA nephropathy (IgAN) is the most common type of glomerulonephritis worldwide, which follows a chronic but nonetheless highly variable course of progression. IgA immune complexes are the primary source of renal deposits in IgAN. Apart from the presence of granular IgA1 deposits in the glomerular mesangium and mesangial hypercellularity as common features, the detailed process of IgA1 deposition and clearance in the kidney remains unclear. We sought to examine the dynamics of IgA deposition and tissue plasticity in response to deposits including their intrarenal clearance. We followed a synthetic approach to produce a recombinant fusion between IgA Fc (rIgA) and a biotin tag, which was subsequently induced with streptavidin (SA) to form an oligomeric poly-IgA mimic. Both uninduced rIgA (mono-rIgA) and polymeric SA-rIgA (poly-rIgA) were injected intravenously into Wistar rats. Plasma IgA levels and renal and liver histology were examined in a time series. In contrast to mono-rIgA, this synthetic poly-rIgA analog formed renal deposits exclusively in the glomerulus and were mostly cleared in 3 h. However, repeated daily injections for 12 days caused long-lasting and stronger glomerular IgA deposition together with IgG and complement C3, in association with mesangial cell proliferation, matrix expansion, and variable degrees of albuminuria and hematuria that phenocopied IgAN. Ex vivo, poly-rIgA bound cultured mesangial cells and elicited cytokine production, in addition to activating plasma C3 that was consistent with the actions of IgA immune complexes in IgAN pathogenesis. Remarkably, the kidneys were able to reverse all pathologic manifestations and restore normal glomerular histology 2 weeks after injections were halted. The synthetic model showed the kinetics between the intricate balance of renal deposition and clearance, as well as glomerular plasticity towards healing. Together, the results revealed a priming effect of existing deposits in promoting stronger and longer-lasting IgA deposition to cause renal damage.
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影响因子：
15
作者：
Kitov, PI;Bundle, DR
通讯作者：
Bundle, DR
影响因子：
19.6
作者：
IMAI, H;NAKAMOTO, Y;MIURA, AB
通讯作者：
MIURA, AB
影响因子：
81.5
作者：
Lai, Kar Neng;Tang, Sydney C. W.;Glassock, Richard J.
通讯作者：
Glassock, Richard J.
DOI：
10.1007/978-1-4939-2272-7_12
发表时间：
2015
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Fairhead, Michael;Howarth, Mark
通讯作者：
Howarth, Mark
影响因子：
12.8
作者：
Moldoveanu Z;Suzuki H;Reily C;Satake K;Novak L;Xu N;Huang ZQ;Knoppova B;Khan A;Hall S;Yanagawa H;Brown R;Winstead CJ;O'Quinn DB;Weinmann A;Gharavi AG;Kiryluk K;Julian BA;Weaver CT;Suzuki Y;Novak J
通讯作者：
Novak J