Deposition of mannan binding protein and mannan binding protein-mediated complement activation in the glomeruli of patients with IgA nephropathy
Deposition of mannan binding protein and mannan binding protein-mediated complement activation in the glomeruli of patients with IgA nephropathy
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DOI：
10.1159/000045212
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发表时间：
1998-12-01
期刊：
影响因子：
2.5
通讯作者：
Makino, H
中科院分区：
文献类型：
--
作者：
Matsuda, M;Shikata, K;Makino, H
甘露聚糖结合蛋白（MBP）是一种C型凝集素，对甘露糖和N-乙酰葡糖胺具有高亲和力。还已知在没有C1组分的情况下激活C4和C2，这被称为“凝集素途径”。我们现在报告的存在MBP和MBP介导的补体激活伊加肾病患者的肾小球使用免疫组化方法。在42例伊加肾病患者中，7例在肾小球系膜区检测到MBP，并与IgA 1共定位。在19例其他类型的IC介导的肾小球肾炎（包括狼疮性肾炎和膜性肾病）或无肾炎的患者中，肾小球中未检测到MBP。伊加肾病MBP阳性组C2和/或C4阳性率为87.5%，阴性组为20%。此外，与MBP阴性病例相比，MBP阳性病例表现出明显的系膜细胞增殖、较低的肌酐清除率（53.4 +/- 10.0 vs. 77.8 +/- 4.7 ml/min）和较高的尿蛋白排泄量（2.5 +/- 0.9 vs. 0.9 +/- 0.2 g/d）。这些结果表明，MBP通过凝集素途径参与肾小球补体激活，从而导致伊加肾病肾小球损伤。由于伊加肾病患者IgA 1分子的寡糖链改变，如唾液酸和半乳糖减少，MBP可能通过与糖链之间的相互作用与IgA 1分子结合。
Mannan binding protein (MBP) is a C-type lectin and has a high affinity to mannose and N-acetyl glucosamine. It is also known to activate C4 and C2 without C1 component, which is called 'lectin pathway'. We now report the presence of MBP and MBP-mediated complement activation in renal glomeruli of IgA nephropathy patients using an immunohistochemical method. In 7 of 42 cases with IgA nephropathy, MBP was detected in the glomerular mesangial area and colocalized with IgA1. In 19 cases with other types of IC-mediated glomerulonephritis including lupus nephritis and membranous nephropathy or without nephritis, MBP was not detected in the glomerulus. The C2- and/or C4-positive rate was 87.5% in the MBP-positive group and 20% in the MBP-negative group of IgA nephropathy. In addition, MBP-positive cases showed marked mesangial cell proliferation, lower creatinine clearance (53.4 +/- 10.0 vs. 77.8 +/- 4.7 ml/min) and higher urinary protein excretion (2.5 +/- 0.9 vs. 0.9 +/- 0.2 g/day) compared with MBP-negative cases. These findings suggested that MBP was involved in glomerular complement activation through the lectin pathway and thus induced glomerular injury of IgA nephropathy. Since oligosaccharide chain alterations such as reduced sialic acid and galactose of IgA1 molecule have been reported in IgA nephropathy patients, MBP might bind to the IgA1 molecule via interaction between MBP and sugar chain.