A Branched and Double Alpha-Gal-Bearing Synthetic Neoglycoprotein as a Biomarker for Chagas Disease.
A Branched and Double Alpha-Gal-Bearing Synthetic Neoglycoprotein as a Biomarker for Chagas Disease.
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DOI：
10.3390/molecules27175714
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发表时间：
2022-09-05
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恰加斯病（CD）是由寄生虫克氏锥虫引起的，影响全世界600万至700万人。诊断仍然是具有挑战性的，由于广泛的寄生虫的多样性，包括7种基因型（TcI-VI和Tcbat），具有不同的生态流行病学，生物学和病理学特征。化疗干预通常是有效的，但与严重的不良事件。由于缺乏用于早期评估治疗结果的生物标志物（BMK），更安全，更有效的治疗方法的开发受到阻碍。哺乳动物寄生锥鞭虫阶段表达糖基磷脂酰肌醇锚定粘蛋白（tGPI-MUC），其O-聚糖主要由末端非还原性α-吡喃半乳糖基（α-Gal）糖表位分支。这些在人体中不存在，因此具有高度免疫原性，是特异性CD抗α-Gal抗体的诱导剂。为了寻找基于α-Gal的BMK，本文描述了新糖蛋白NGP 11b的合成，其由用支链三糖Galα（1，2）[Galα（1，6）]Galβ修饰的载体蛋白组成。采用委内瑞拉和墨西哥的慢性CD（CCD）患者和健康对照的血清/血浆进行荧光免疫测定，NGP 11 b显示出与来自基因型TcI的tGPI-MUC相似的灵敏度和特异性，在这些国家占主导地位。对接受化疗的CCD患者的初步评价显示，抗α-Gal抗体对NGP 11 b的反应性显著降低。我们的数据表明，NGP 11b是一个潜在的BMK的诊断和治疗评估CCD患者。
Chagas disease (CD) is caused by the parasite Trypanosoma cruzi and affects 6–7 million people worldwide. The diagnosis is still challenging, due to extensive parasite diversity encompassing seven genotypes (TcI-VI and Tcbat) with diverse ecoepidemiological, biological, and pathological traits. Chemotherapeutic intervention is usually effective but associated with severe adverse events. The development of safer, more effective therapies is hampered by the lack of biomarker(s) (BMKs) for the early assessment of therapeutic outcomes. The mammal-dwelling trypomastigote parasite stage expresses glycosylphosphatidylinositol-anchored mucins (tGPI-MUC), whose O-glycans are mostly branched with terminal, nonreducing α-galactopyranosyl (α-Gal) glycotopes. These are absent in humans, and thus highly immunogenic and inducers of specific CD anti-α-Gal antibodies. In search for α-Gal-based BMKs, here we describe the synthesis of neoglycoprotein NGP11b, comprised of a carrier protein decorated with the branched trisaccharide Galα(1,2)[Galα(1,6)]Galβ. By chemiluminescent immunoassay using sera/plasma from chronic CD (CCD) patients from Venezuela and Mexico and healthy controls, NGP11b exhibited sensitivity and specificity similar to that of tGPI-MUC from genotype TcI, predominant in those countries. Preliminary evaluation of CCD patients subjected to chemotherapy showed a significant reduction in anti-α-Gal antibody reactivity to NGP11b. Our data indicated that NGP11b is a potential BMK for diagnosis and treatment assessment in CCD patients.
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影响因子：
4.1
作者：
ALMEIDA, IC;FERGUSON, MAJ;TRAVASSOS, LR
通讯作者：
TRAVASSOS, LR
影响因子：
2.2
作者：
GAZZINELLI, RT;PEREIRA, MES;BRENER, Z
通讯作者：
BRENER, Z
影响因子：
2.9
作者：
Almeida, IC;Covas, DT;Travassos, LR
通讯作者：
Travassos, LR
影响因子：
2.7
作者：
Alarcon de Noya, Belkisyole;Gonzalez, Oscar Noya
通讯作者：
Gonzalez, Oscar Noya
影响因子：
11.8
作者：
Bern, Caryn;Montgomery, Susan P.
通讯作者：
Montgomery, Susan P.