Serological diagnostics is generally defined as the detection of specific human immunoglobulins developed against viral, bacterial, or parasitic diseases. Serological tests facilitate the detection of past infections, evaluate immune status, and provide prognostic information. Serological assays were traditionally implemented as indirect immunoassays, and their design has not changed for decades. The advantages of straightforward setup and manufacturing, analytical sensitivity and specificity, affordability, and high-throughput measurements were accompanied by limitations such as semi-quantitative measurements, lack of universal reference standards, potential cross-reactivity, and challenges with multiplexing the complete panel of human immunoglobulin isotypes and subclasses. Redesign of conventional serological tests to include multiplex quantification of immunoglobulin isotypes and subclasses, utilize universal reference standards, and minimize cross-reactivity and non-specific binding will facilitate the development of assays with higher diagnostic specificity. Improved serological assays with higher diagnostic specificity will enable screenings of asymptomatic populations and may provide earlier detection of infectious diseases, autoimmune disorders, and cancer. In this review, we present the major clinical needs for serological diagnostics, overview conventional immunoassay detection techniques, present the emerging immunoassay detection technologies, and discuss in detail the advantages and limitations of mass spectrometry and immunoaffinity proteomics for serological diagnostics. Finally, we explore the design of novel immunoaffinity-proteomic assays to evaluate cell-mediated immunity and advance the sequencing of clinically relevant immunoglobulins.

中文翻译：

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用免疫亲和蛋白质组学重新定义血清学诊断

血清学诊断通常被定义为针对病毒、细菌或寄生虫疾病开发的特定人类免疫球蛋白的检测。血清学测试有助于检测过去的感染、评估免疫状态并提供预后信息。血清学检测传统上是作为间接免疫检测进行的，其设计几十年来一直没有改变。简单的设置和制造、分析灵敏度和特异性、经济性和高通量测量的优点也伴随着一些局限性，例如半定量测量、缺乏通用参考标准、潜在的交叉反应性以及多重检测的完整面板的挑战。人免疫球蛋白同种型和亚类。重新设计传统血清学测试，包括免疫球蛋白同种型和亚类的多重定量，利用通用参考标准，并最大限度地减少交叉反应和非特异性结合，将有助于开发具有更高诊断特异性的检测方法。具有更高诊断特异性的改进血清学检测将能够筛查无症状人群，并可能提供传染病、自身免疫性疾病和癌症的早期检测。在这篇综述中，我们介绍了血清学诊断的主要临床需求，概述了传统的免疫分析检测技术，介绍了新兴的免疫分析检测技术，并详细讨论了质谱和免疫亲和蛋白质组学用于血清学诊断的优点和局限性。最后，我们探索了新型免疫亲和蛋白质组检测的设计，以评估细胞介导的免疫并推进临床相关免疫球蛋白的测序。