Anti-GM1/GD1a complex antibodies in GBS sera specifically recognize the hybrid dimer GM1-GD1a
Anti-GM1/GD1a complex antibodies in GBS sera specifically recognize the hybrid dimer GM1-GD1a
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DOI：
10.1093/glycob/cwr139
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发表时间：
2012-03-01
期刊：
影响因子：
4.3
通讯作者：
Sonnino, Sandro
中科院分区：
文献类型：
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作者：
Mauri, Laura;Casellato, Riccardo;Sonnino, Sandro
一些格林-巴利综合征(GBS)患者的抗体识别由两种不同的神经节苷脂形成的抗原表位，即神经节苷脂复合体(GSC)，这一新概念现已出现。我们制备了二聚体GM1-GD1a杂化神经节苷脂衍生物，它含有两个结构不同的寡糖链来模拟GSC。我们使用该化合物对GBS患者的血清进行了高效薄层分析、免疫染色和酶联免疫吸附试验。我们还合成了GM1-GM1和GD1a-GD1a二聚体化合物，并与天然神经节苷脂一起用于对照实验。混合二聚体GM1-GD1a被来自GBS患者的人血清特异性识别，这些患者产生了针对分组复杂寡糖的抗寡糖抗体，证实了GBS患者产生了针对GSC的抗体的信息。高分辨H-1-C-13异核单量子相干-核Overhauser效应谱核磁共振实验表明，GM1的IV Gal-H1和GD1a的IV Gal-H2之间存在相互作用，表明二聚体神经节苷脂的两条寡糖链形成了单一抗体结构域识别的单一表位。一种能够制备几种杂交神经节苷脂的方法的可用性，以及简单分析方法的可用性，为理解和治疗几种神经疾病开辟了新的视角。
It is now emerging the new concept that the antibodies from some patients with Guillain-Barre syndrome (GBS) recognize an antigenic epitope formed by two different gangliosides, a ganglioside complex (GSC). We prepared the dimeric GM1-GD1a hybrid ganglioside derivative that contains two structurally different oligosaccharide chains to mimic the GSC. We use this compound to analyze sera from GBS patients by high-performance thin-layer chromatography immunostaining and enzyme-linked immunosorbent assay. We also synthesized the dimeric GM1-GM1 and GD1a-GD1a compounds that were used in control experiments together with natural gangliosides. The hybrid dimeric GM1-GD1a was specifically recognized by human sera from GBS patients that developed anti-oligosaccharide antibodies specific for grouped complex oligosaccharides, confirming the information that GBS patients developed antibodies against a GSC. High-resolution H-1-C-13 heteronuclear single-quantum coherence-nuclear overhauser effect spectroscopy nuclear magnetic resonance experiments showed an interaction between the IV Gal-H1 of GM1 and the IV Gal-H2 of GD1a suggesting that the two oligosaccharide chains of the dimeric ganglioside form a single epitope recognized by a single-antibody domain. The availability of a method capable to prepare several hybrid gangliosides, and the availability of simple analytical approaches, opens new perspectives for the understanding and the therapy of several neuropathies.