Glomerular activation of the lectin pathway of complement in IgA nephropathy is associated with more severe renal disease
Glomerular activation of the lectin pathway of complement in IgA nephropathy is associated with more severe renal disease
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DOI：
10.1681/asn.2005090923
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发表时间：
2006-06-01
影响因子：
13.6
通讯作者：
Daha, MR
中科院分区：
文献类型：
--
作者：
Roos, A;Rastaldi, MP;Daha, MR
伊加肾病（IgAN）的特征在于伊加和补体成分的肾小球共沉积。早期的研究表明，伊加激活补体的旁路途径，而最近的数据也表明凝集素途径的激活。凝集素途径可以通过甘露糖结合凝集素（MBL）和纤维胶凝蛋白与碳水化合物配体的结合来激活，然后激活MBL相关的丝氨酸蛋白酶和C4。本研究探讨了凝集素途径在IgAN中的潜在作用。IgAN患者的肾活检（n = 60）显示IgA 1，但不IgA 2系膜沉积。60例IgAN中15例（25%）肾小球内有MBL沉积，呈系膜型。所有MBL阳性病例，但没有MBL阴性病例显示L-纤维胶凝蛋白、MBL相关丝氨酸蛋白酶和C4d的球蛋白共沉积。MBL和L-纤维胶凝蛋白的肾小球沉积与更明显的组织学损伤相关，如肾小球系膜增生、毛细血管外增生、肾小球硬化和间质浸润增加以及蛋白尿显著增加所证明。伴或不伴肾小球MBL沉积的IgAN患者的血清MBL、L-纤维胶凝蛋白或伊加水平或循环伊加的大小分布均无显著差异。此外，体外实验显示MBL与多聚体而非单体伊加明确结合，两组之间无显著差异。总之，这些发现强烈地指出补体的凝集素途径在IgAN中的肾小球补体活化中的作用，并表明MBL和L-纤维胶凝蛋白在疾病进展中的贡献。
IgA nephropathy (IgAN) is characterized by glomerular co-deposition of IgA and complement components. Earlier studies showed that IgA activates the alternative pathway of complement, whereas more recent data also indicate activation of the lectin pathway. The lectin pathway can be activated by binding of mannose-binding lectin (MBL) and ficolins to carbohydrate ligands, followed by activation of MBL-associated serine proteases and C4. This study examined the potential role of the lectin pathway in IgAN. Renal biopsies of patients with IgAN (n = 60) showed mesangial deposition of IgA1 but not IgA2. Glonterular deposition of MBL was observed in 15 (25%) of 60 cases with IgAN and showed a mesangial pattern. All MBL-positive case, but none of the MBL-negative cases showed glonterular co-deposition of L-ficolin, MBL-associated serine proteases, and C4d. Glomerular deposition of MBL and L-ficolin was associated with more pronounced histologic damage, as evidenced by increased mesangial proliferation, extracapillary proliferation, glomerular sclerosis, and interstitial infiltration, as well as with significantly more proteinuria. Patients who had IgAN with or without glomerular MBL deposition did not show significant differences in serum levels of MBL, L-ficolin, or IgA or in the size distribution of circulating IgA. Furthermore, in vitro experiments showed clear binding of MBL to polymeric but not monomeric patient IgA, without a significant difference between both groups. Together, these findings strongly point to a role for the lectin pathway of complement in glomerular complement activation in IgAN and suggest a contribution for both MBL and L-ficolin in the progression of the disease.