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评估 IgG3 作为疟疾传播强度中高度地区疟原虫血清学暴露标志物的应用。

Assessment of IgG3 as a serological exposure marker for in areas with moderate-high malaria transmission intensity.

机构信息

Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia.

Department of Medical Biology, University of Melbourne, Melbourne, VIC, Australia.

出版信息

Front Cell Infect Microbiol. 2022 Aug 9;12:950909. doi: 10.3389/fcimb.2022.950909. eCollection 2022.

Abstract

A more sensitive surveillance tool is needed to identify infections for treatment and to accelerate malaria elimination efforts. To address this challenge, our laboratory has developed an eight-antigen panel that detects total IgG as serological markers of exposure within the prior 9 months. The value of these markers has been established for use in areas with low transmission. In moderate-high transmission areas, there is evidence that total IgG is more long-lived than in areas with low transmission, resulting in poorer performance of these markers in these settings. Antibodies that are shorter-lived may be better markers of recent infection for use in moderate-high transmission areas. Using a multiplex assay, the antibody temporal kinetics of total IgG, IgG1, IgG3, and IgM against 29 P antigens were measured over 36 weeks following asymptomatic infection in Papua New Guinean children ( = 31), from an area with moderate-high transmission intensity. IgG3 declined faster to background than total IgG, IgG1, and IgM. Based on these kinetics, IgG3 performance was then assessed for classifying recent exposure in a cohort of Peruvian individuals ( = 590; age 3-85 years) from an area of moderate transmission intensity. Using antibody responses against individual antigens, the highest performance of IgG3 in classifying recent infections in the prior 9 months was to one of the Pv-fam-a proteins assessed (PVX_125728) (AUC = 0.764). Surprisingly, total IgG was overall a better marker of recent infection, with the highest individual classification performance to RBP2b (PVX_094255) (AUC = 0.838). To understand the acquisition of IgG3 in this Peruvian cohort, relevant epidemiological factors were explored using a regression model. IgG3 levels were positively associated with increasing age, living in an area with (relatively) higher transmission intensity, and having three or more PCR-detected blood-stage infections within the prior 13 months. Overall, we found that IgG3 did not have high accuracy for detecting recent exposure to in the Peruvian cohort, with our data suggesting that this is due to the high levels of prior exposure required to acquire high IgG3 antibody levels.

摘要

需要更敏感的监测工具来识别感染,以便进行治疗,并加速消除疟疾的努力。为了应对这一挑战,我们的实验室开发了一个包含 8 种抗原的面板,可检测过去 9 个月内总 IgG 作为暴露的血清学标志物。这些标志物的价值已在低传播地区得到确立。在中高传播地区,有证据表明总 IgG 的寿命比低传播地区长,导致这些标志物在这些环境中的性能较差。寿命较短的抗体可能是中高传播地区近期感染的更好标志物。我们使用多重分析,在巴布亚新几内亚儿童(n = 31)无症状感染后 36 周内测量了针对 29 种 P 抗原的总 IgG、IgG1、IgG3 和 IgM 的抗体时间动态,这些儿童来自中高传播强度地区。与总 IgG、IgG1 和 IgM 相比,IgG3 更快地下降到背景水平。基于这些动力学,我们评估了 IgG3 在秘鲁人群队列(n = 590;年龄 3-85 岁)中的近期暴露分类中的表现,这些人群来自中传播强度地区。使用针对单个抗原的抗体反应,在过去 9 个月内对最近感染进行分类时,IgG3 对评估的 Pv-fam-a 蛋白之一(PVX_125728)的表现最高(AUC = 0.764)。令人惊讶的是,总 IgG 总体上是最近感染的更好标志物,与 RBP2b(PVX_094255)的个体分类性能最高(AUC = 0.838)。为了了解 IgG3 在秘鲁队列中的获得情况,我们使用回归模型探讨了相关的流行病学因素。IgG3 水平与年龄增长、生活在(相对)高传播强度地区以及在过去 13 个月内有三次或更多次 PCR 检测到的血期感染呈正相关。总体而言,我们发现 IgG3 对检测秘鲁人群中的近期疟原虫暴露没有高准确性,我们的数据表明,这是由于获得高 IgG3 抗体水平所需的先前暴露水平较高所致。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2947/9395743/56dca87da342/fcimb-12-950909-g001.jpg

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