Chemoenzymatic Synthesis of Campylobacter jejuni Lipo-oligosaccharide Core Domains to Examine Guillain-Barré Syndrome Serum Antibody Specificities.
Chemoenzymatic Synthesis of Campylobacter jejuni Lipo-oligosaccharide Core Domains to Examine Guillain-Barré Syndrome Serum Antibody Specificities.
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DOI：
10.1021/jacs.0c08583
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发表时间：
2020-11-18
影响因子：
15
通讯作者：
Boons GJ
中科院分区：
文献类型：
--
作者：
Li T;Wolfert MA;Wei N;Huizinga R;Jacobs BC;Boons GJ
格林-巴罗综合征通常是由空肠弯曲杆菌感染引起的，这种感染诱导了对脂寡糖（LOS）的抗体，这种抗体与周围神经的神经节苷交叉反应，导致多发性神经病变。为了检测抗神经节苷脂抗体的精细特异性，并开发一个更强大的诊断和疾病监测平台，我们开发了一种化学酶方法，提供了一个前所未有的由各种神经节苷脂模拟物延伸的空肠C. LOS内核组成的低聚糖面板。将化合物和相应的神经节寡糖作为芯片打印，检测凝集素、抗神经节苷脂抗体和GBS患者血清抗体的结合特异性。虽然凝集素和抗神经节苷脂抗体不能区分神经节寡糖和模拟物，但患者血清样品与神经节苷脂模拟物结合更强。这些数据表明，抗体被诱导到一个包含细菌LOS特有的庚基残基的外源表位上，这些抗体随后与神经节苷脂发生低亲和力的交叉反应。该芯片检测抗gm1a抗体具有高灵敏度，将在诊断、疾病监测和免疫学研究中具有吸引力。
Guillain–Barré syndrome is often caused by Campylobacter jejuni infection that has induced antibodies to the lipo-oligosaccharide (LOS) that cross-react with gangliosides at peripheral nerves causing polyneuropathy. To examine fine specificities of anti-ganglioside antibodies and develop a more robust platform for diagnosis and disease monitoring, we developed a chemoenzymatic approach that provided an unprecedented panel of oligosaccharides composed of the inner-core of the LOS of C. jejuni extended by various ganglioside mimics. The compounds and corresponding ganglio-oligosaccharides were printed as a microarray to examine binding specificities of lectins, anti-ganglioside antibodies, and serum antibodies of GBS patients. Although lectins and anti-ganglioside antibodies did not differentiate the ganglio-oligosaccharides and mimics, the patient serum samples bound much more strongly to the ganglioside mimics. The data indicate that antibodies have been elicited to a foreign epitope that includes a heptosyl residue unique of bacterial LOS and that these antibodies subsequently cross-react with lower affinity to gangliosides. The microarray detected anti-GM1a antibodies with high sensitivity and will be attractive for diagnosis, disease monitoring, and immunological research.
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影响因子：
38.1
作者：
Goodfellow, John A.;Willison, Hugh J.
通讯作者：
Willison, Hugh J.
影响因子：
3.1
作者：
Blixt, O;Vasiliu, D;Wakarchuk, W
通讯作者：
Wakarchuk, W
影响因子：
9.9
作者：
Kusunoki, S;Iwamori, M;Kanazawa, I
通讯作者：
Kanazawa, I
影响因子：
1.8
作者：
Liu, MZ;Yu, B;Hui, YZ
通讯作者：
Hui, YZ
影响因子：
4.8
作者：
Gilbert, M;Brisson, JR;Wakarchuk, WW
通讯作者：
Wakarchuk, WW