IgA glycosylation and IgA immune complexes in the pathogenesis of IgA nephropathy

被引:181
作者
Novak, Jan [1 ]
Julian, Bruce A. [1 ,2 ]
Tomono, Milan [2 ]
Mestecky, Jiri [1 ,2 ,3 ]
机构
[1] Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA
[2] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA
[3] Charles Univ Prague, Inst Microbiol & Immunol, Prague, Czech Republic
关键词
IgA nephropathy; glycosylation; IgA1; O-glycans;
D O I
10.1016/j.semnephrol.2007.10.009
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Circulating immune complexes containing aberrantly glycosylated IgA1 play a pivotal role in the pathogenesis of IgA nephropathy (IgAN). A portion of IgA1 secreted by IgA1-producing cells in patients with IgAN is galactose-deficient and consequently recognized by anti-glycan IgG or IgA1 antibodies. Some of the resultant immune complexes in the circulation escape normal clearance mechanisms, deposit in the renal mesangium, and induce glomerular injury. Recent studies of the origin of these aberrant molecules, their glycosylation profiles, and mechanisms of biosynthesis have provided new insight into the autoimmune nature of the pathogenesis of this common renal disease. An imbalance in the activities of the pertinent glycosyltransferases in the IgA1-producing cells favors production of molecules with galactose-deficient O-linked glycans at specific sites in the hinge region of the α heavy chains. By using sophisticated analytic methods, it may be possible to define biomarkers for diagnostic purposes and identify new therapeutic targets for a future disease-specific therapy. © 2008 Elsevier Inc. All rights reserved.
引用
收藏
页码:78 / 87
页数:10
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