Pathogenetic significance of aberrant glycosylation of IgA1 in IgA nephropathy
Pathogenetic significance of aberrant glycosylation of IgA1 in IgA nephropathy
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DOI：
10.1007/s10157-008-0054-5
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发表时间：
2008-10-01
影响因子：
2.3
通讯作者：
Gejyo, Fumitake
中科院分区：
文献类型：
--
作者：
Narita, Ichiei;Gejyo, Fumitake
IgA肾病（IgAN）是世界范围内最常见的原发性肾小球肾炎形式，其定义为肾小球系膜中主要的IgA1沉积。在迄今为止报道的IgAN中IgA免疫系统的异常中，IgA1铰链区异常的o -连锁糖基化是最一致的发现。在血清、扁桃体淋巴细胞和系膜沉积物的洗脱液中发现了携带异常糖基化的IgA1分子，其特征是o -连接的n -乙酰半乳糖胺残基减少，伴有或不伴有o -连接糖的末端唾液化改变。半乳糖基化不完全的IgA1倾向于通过自聚集或免疫复合物的形成在肾小球系膜中积累。暴露于这些IgA1免疫复合物的肾小球系膜细胞可以增殖并分泌细胞因子、趋化因子、生长因子和促进肾小球炎症反应的细胞外基质成分。虽然编码参与o糖基化过程的酶的基因，如C1GALT1，已被报道对IgAN易感性负责，但最近的证据表明，这种异常仅限于一小部分B细胞群，并且是由粘膜免疫系统中IgA1产生和分泌失调引起的。本文将重点讨论IgA1 o -半乳糖基化不完全性在IgAN发病中的作用，并提出IgA1异常在IgAN中发生的可能机制。
IgA nephropathy (IgAN), the most common form of primary glomerulonephritis worldwide, is defined by predominant IgA1 deposits in the glomerular mesangium. Among abnormalities of the IgA immune system reported so far in IgAN, aberrant O-linked glycosylation in the hinge region of IgA1 is the most consistent finding. IgA1 molecules bearing abnormal glycosylation have been found in serum, in tonsillar lymphocytes, and in eluate from mesangial deposits, and characterized by decreased O-linked N-acetylgalactosamine residues with or without alteration in the terminal sialylation of the O-linked sugars. IgA1 with incomplete galactosylation has a tendency to accumulate in glomerular mesangium by self-aggregation or immune complex formation. Glomerular mesangial cells exposed to immune complexes of these IgA1 can proliferate and secrete cytokines, chemokines, growth factors, and extracellular matrix components promoting inflammatory reactions in the glomeruli. Although genes encoding enzymes involved in the O-glycosylation process, such as C1GALT1, have been reported to be responsible for susceptibility to IgAN, recent evidence suggests that the abnormality is restricted to a small fraction of B cell populations and arises from dysregulated IgA1 production and secretion in mucosal immune system. This review will focus on and discuss the role of incompleteness of IgA1 O-galactosylation in the pathogenesis of IgAN and propose a possible mechanism in which abnormal IgA1 occurs in IgAN.