IgA nephropathy and IgA vasculitis with nephritis have a shared feature involving galactose-deficient IgA1-oriented pathogenesis
IgA nephropathy and IgA vasculitis with nephritis have a shared feature involving galactose-deficient IgA1-oriented pathogenesis
复制标题
DOI：
10.1016/j.kint.2017.10.019
复制
发表时间：
2018-03-01
影响因子：
19.6
通讯作者：
Suzuki, Yusuke
中科院分区：
文献类型：
--
作者：
Suzuki, Hitoshi;Yasutake, Junichi;Suzuki, Yusuke
半乳糖缺乏的IgA1已被认为是IgA肾病(IgAN)的重要效应分子。我们先前发现，半乳糖缺乏的IgA1特异性单抗KM55可以检测到IgAN患者循环中的半乳糖缺乏的IgA1，使我们能够研究半乳糖缺乏的IgA1的分子作用。在此，我们进一步用KM55免疫组织化学方法检测了IgAN患者肾小球沉积中半乳糖缺乏的IgA1的病理生理学意义。对48例IgAN患者和49例其他肾脏疾病如狼疮性肾炎、丙型肝炎病毒相关性肾病、IgA血管炎伴肾炎(IgA-VN)和膜性肾病患者的肾活检标本石蜡切片进行半乳糖缺陷型IgA1 KM55免疫组织化学染色。肾小球半乳糖缺陷型IgA1在IgAN和IgA-VN中特异性表达，而在其他肾脏疾病中未见表达。半乳糖缺乏的IgA1主要定位于系膜区，表现为IgA沉积。但在狼疮性肾炎伴肾小球IgA沉积的患者中未检测到半乳糖缺乏的IgA1。因此，我们的研究强烈表明，IgAN和IgA-VN在半乳糖缺乏的IgA1导向的发病机制上具有共同的特征。
Galactose-deficient IgA1 has been proposed as an important effector molecule in IgA nephropathy (IgAN). We previously showed that the galactose-deficient IgA1-specific monoclonal antibody KM55 can detect circulating galactose-deficient IgA1 in patients with IgAN, enabling us to study the molecular roles of galactose-deficient IgA1. Herein, we further examined the pathophysiological significance of galactose-deficient IgA1 in glomerular deposits of patients with IgAN by immunohistochemistry using KM55. Immunostaining of galactose-deficient IgA1 with KM55 was performed in paraffin-embedded sections of renal biopsy specimens from 48 patients with IgAN and 49 patients with other renal diseases such as lupus nephritis, HCV-related nephropathy, IgA vasculitis with nephritis (IgA-VN), and membranous nephropathy. Glomerular galactose-deficient IgA1 was specifically detected in IgAN and IgA-VN but not in the other renal diseases. Galactose-deficient IgA1 was localized predominantly in the mesangial region as IgA deposition. However, galactose-deficient IgA1 was not detected in patients with lupus nephritis accompanied by glomerular IgA deposition. Thus, our study strongly suggests that IgAN and IgA-VN have a shared feature regarding galactose-deficient IgA1-oriented pathogenesis.