Recognition of galactose-deficient O-glycans in the hinge region of IgA1 by N-acetylgalactosamine-specific snail lectins: a comparative binding study.
Recognition of galactose-deficient O-glycans in the hinge region of IgA1 by N-acetylgalactosamine-specific snail lectins: a comparative binding study.
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DOI：
10.1021/bi9019498
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发表时间：
2010-07-13
期刊：
影响因子：
2.9
通讯作者：
Herr, Andrew B.
中科院分区：
文献类型：
--
作者：
Gomes, Michelle M.;Suzuki, Hitoshi;Brooks, Monica T.;Tomana, Milan;Moldoveanu, Zina;Mestecky, Jiri;Julian, Bruce A.;Novak, Jan;Herr, Andrew B.
IgA 1糖基化的异常与伊加肾病（IgAN）的发病机制有关，IgA肾病是一种以含IgA 1的免疫复合物在肾小球系膜中沉积为特征的肾脏疾病。来自IgAN患者的IgA 1的特征是铰链区存在半乳糖（Gal）缺陷的O-聚糖，可以充当抗聚糖IgG或IgA 1抗体的表位。产生的循环免疫复合物被捕获在肾脏的肾小球系膜中，在那里它们通过激活系膜细胞触发局部炎症反应。某些凝集素识别缺乏半乳糖的IgA 1上的末端N-乙酰半乳糖胺（GalNAc）含O-聚糖，并可能用作诊断工具。为了更好地了解这些凝集素的GalNAc识别，我们进行了结合研究，以评估半乳糖凝集素（HAA）和苹果凝集素（HPA）与半乳糖缺乏型IgA 1的相互作用。表面等离子体共振光谱显示，HAA和HPA结合到半乳糖缺乏的合成铰链区糖肽（HR-GalNAc）以及各种异常糖基化的IgA 1骨髓瘤蛋白。尽管有六个结合位点，但HAA和HPA都以功能性二价方式结合IgA 1，对IgA 1的表观亲和力与IgA 1铰链中暴露的GalNAc基团的数量有关。最后，HAA和HPA显示出非常有效地区分IgA 1分泌的细胞系来源于IgA肾病患者和健康对照的外周血细胞。这些研究提供了深入了解凝集素识别的半乳糖缺陷型IgA 1铰链区，并奠定了基础，为发展可靠的诊断工具IgAN。
Aberrancies in IgA1 glycosylation have been linked to the pathogenesis of IgA nephropathy (IgAN), a kidney disease characterized by deposits of IgA1-containing immune complexes in the glomerular mesangium. IgA1 from IgAN patients is characterized by the presence of galactose (Gal)-deficient O-glycans in the hinge region that can act as epitopes for anti-glycan IgG or IgA1 antibodies. The resulting circulating immune complexes are trapped in the glomerular mesangium of the kidney where they trigger localized inflammatory responses by activating mesangial cells. Certain lectins recognize the terminal N-acetylgalactosamine (GalNAc)-containing O-glycans on Gal-deficient IgA1 and can be potentially used as diagnostic tools. To better understand GalNAc recognition by these lectins, we have carried out binding studies to assess the interaction of Helix aspersa agglutinin (HAA) and Helix pomatia agglutinin (HPA) with Gal-deficient IgA1. Surface plasmon resonance spectroscopy revealed that both HAA and HPA bind to a Gal-deficient synthetic hinge-region glycopeptide (HR-GalNAc) as well as various aberrantly glycosylated IgA1 myeloma proteins. Despite having six binding sites, both HAA and HPA bind IgA1 in a functionally bivalent manner, with the apparent affinity for IgA1 related to the number of exposed GalNAc groups in the IgA1 hinge. Finally, HAA and HPA were shown to discriminate very effectively between the IgA1 secreted by cell lines derived from peripheral blood cells of patients with IgAN and of healthy controls. These studies provide insight into lectin recognition of the Gal-deficient IgA1 hinge region and lay the groundwork for the development of reliable diagnostic tools for IgAN.
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影响因子：
4.8
作者：
Herr, AB;Ornitz, DM;Waksman, G
通讯作者：
Waksman, G
影响因子：
5.6
作者：
Herr, AB;White, CL;Bjorkman, PJ
通讯作者：
Bjorkman, PJ
影响因子：
13.2
作者：
Lasseur, C;Allen, AC;Combe, C
通讯作者：
Combe, C
影响因子：
6
作者：
Ezaki, T;Baluk, P;McDonald, M
通讯作者：
McDonald, M
DOI：
10.1073/pnas.69.12.3673
发表时间：
1972-01-01
影响因子：
11.1
作者：
FRANGION.B;WOLFENST.C
通讯作者：
WOLFENST.C