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Development of a Multiplex Glycan Microarray Assayand Comparative Analysis of Human Serum Anti-Glycan IgA IgG andIgM Repertoires

机译:多重糖链微阵列测定的开发血清抗聚糖IgAIgG和IgM曲目

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摘要

Serum antibodies that recognize carbohydrate antigens play a fundamental role in immune defense, homeostasis, and autoimmunity. In addition, they serve as potential biomarkers for a variety of medical applications. For most anti-glycan antibodies found in human serum, however, the origins, regulation, and biological significance are not well understood. Antibody subpopulations that are relevant to a particular biological process or disease are often difficult to identify from the myriad of anti-glycan antibodies present in human serum. While prior studies have examined anti-glycan IgG and/or IgM repertoires, little is known about IgA repertoires or how IgA, IgG, and IgM are related. In this study, we describe the development of a multiplex assay to simultaneously detect IgA, IgG, and IgM on a glycan microarray and its application to studying anti-glycan repertoires in healthy subjects. The multiplex glycan microarray assay revealed unique insights and systems-level relationships that would be difficult to uncover using traditional approaches. In particular, we found that anti-glycan IgA, IgG, andIgM expression levels appear to be tightly regulated, coordinatedwithin individuals, and stable over time. Additionally, our resultshelp define natural fluctuations over time, which is critical foridentifying changes that are beyond normal biological variation.
机译:识别碳水化合物抗原的血清抗体在免疫防御,体内平衡和自身免疫中起着基本作用。此外,它们还可以作为多种医学应用的潜在生物标记。然而,对于人类血清中发现的大多数抗聚糖抗体,其起源,调控和生物学意义尚不十分清楚。与特定生物学过程或疾病相关的抗体亚群通常很难从人血清中存在的多种抗聚糖抗体中进行鉴定。尽管先前的研究已经检查了抗聚糖IgG和/或IgM的组成部分,但对IgA组成部分或IgA,IgG和IgM的相关性知之甚少。在这项研究中,我们描述了同时检测糖微阵列上IgA,IgG和IgM的多重检测技术的发展及其在研究健康受试者抗糖类库中的应用。多重聚糖微阵列检测揭示了独特的见解和系统级关系,而使用传统方法很难发现。特别是,我们发现抗聚糖IgA,IgG和IgM表达水平似乎受到严格调节,协调在个人内部,并且随着时间的推移稳定。此外,我们的结果帮助定义随时间变化的自然波动,这对于识别超出正常生物学变异的变化。

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