Carter Michael J, Mitchell Ruth M, Meyer Sauteur Patrick M, Kelly Dominic F, Trück Johannes
Oxford Vaccine Group, Department of Paediatrics, University of Oxford, NIHR Oxford Biomedical Research Centre, Oxford, United Kingdom.
University Children's Hospital, Zurich, Switzerland.
Front Immunol. 2017 Jun 1;8:630. doi: 10.3389/fimmu.2017.00630. eCollection 2017.
Despite the availability of advances in molecular diagnostic testing for infectious disease, there is still a need for tools that advance clinical care and public health. Current methods focus on pathogen detection with unprecedented precision, but often lack specificity. In contrast, the host immune response is highly specific for the infecting pathogen. Serological studies are rarely helpful in clinical settings, as they require acute and convalescent antibody testing. However, the B cell response is much more rapid and short-lived, making it an optimal target for determining disease aetiology in patients with infections. The performance of tests that aim to detect circulating antigen-specific antibody-secreting cells (ASCs) has previously been unclear. Test performance is reliant on detecting the presence of ASCs in the peripheral blood. As such, the kinetics of the ASC response to infection, the antigen specificity of the ASC response, and the methods of ASC detection are all critical. In this review, we summarize previous studies that have used techniques to enumerate ASCs during infection. We describe the emergence, peak, and waning of these cells in peripheral blood during infection with a number of bacterial and viral pathogens, as well as malaria infection. We find that the timing of antigen-specific ASC appearance and disappearance is highly conserved across pathogens, with a peak response between day 7 and day 8 of illness and largely absent following day 14 since onset of symptoms. Data show a sensitivity of ~90% and specificity >80% for pathogen detection using ASC-based methods. Overall, the summarised work indicates that ASC-based methods may be very sensitive and highly specific for determining the etiology of infection and have some advantages over current methods. Important areas of research remain, including more accurate definition of the timing of the ASC response to infection, the biological mechanisms underlying variability in its magnitude and the evolution and the B cell receptor in response to immune challenge. Nonetheless, there is potential of the ASC response to infection to be exploited as the basis for novel diagnostic tests to inform clinical care and public health priorities.
尽管传染病分子诊断检测取得了进展，但仍需要能够推动临床护理和公共卫生发展的工具。当前的方法以前所未有的精度专注于病原体检测，但往往缺乏特异性。相比之下，宿主免疫反应对感染病原体具有高度特异性。血清学研究在临床环境中很少有帮助，因为它们需要急性期和恢复期抗体检测。然而，B细胞反应更快且持续时间更短，使其成为确定感染患者疾病病因的最佳靶点。旨在检测循环抗原特异性抗体分泌细胞（ASC）的检测方法的性能此前尚不清楚。检测性能依赖于在外周血中检测ASC的存在。因此，ASC对感染的反应动力学、ASC反应的抗原特异性以及ASC检测方法都至关重要。在本综述中，我们总结了以前使用技术在感染期间枚举ASC的研究。我们描述了在感染多种细菌和病毒病原体以及疟疾感染期间，这些细胞在外周血中的出现、峰值和消退情况。我们发现，抗原特异性ASC出现和消失的时间在不同病原体中高度保守，在发病第7天至第8天之间反应达到峰值，症状出现后第14天基本消失。数据显示，使用基于ASC的方法检测病原体的灵敏度约为90%，特异性>80%。总体而言，总结的工作表明，基于ASC的方法在确定感染病因方面可能非常敏感且高度特异，并且比当前方法具有一些优势。仍有重要的研究领域，包括更准确地定义ASC对感染反应的时间、其幅度变化背后的生物学机制以及对免疫挑战的B细胞受体的进化。尽管如此，ASC对感染的反应有潜力被用作新型诊断测试的基础，以指导临床护理和公共卫生重点。
