Development of a biomarker signature using grating-coupled fluorescence plasmonic microarray for diagnosis of MIS-C.
Development of a biomarker signature using grating-coupled fluorescence plasmonic microarray for diagnosis of MIS-C.
复制标题
使用光栅耦合荧光等离子微阵列开发生物标志物特征，以诊断MIS-C。
DOI：
10.3389/fbioe.2023.1066391
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发表时间：
2023
影响因子：
5.7
通讯作者：
中科院分区：
文献类型：
--
作者：
儿童多系统炎症综合征（MIS-C）是一种罕见但严重的疾病，可在学龄儿童感染SARS-CoV-2后4-6周发展。到目前为止，在美国已发现超过8，862例MIS-C病例，并已发生72例死亡。这种综合征通常影响5-13岁的儿童; 57%是西班牙裔/拉丁裔/黑人/非西班牙裔，61%的患者是男性，100%的患者要么检测出SARS-CoV-2阳性，要么与COVID-19患者直接接触。不幸的是，MIS-C的诊断是困难的，延误诊断可能导致心源性休克，重症监护入院，延长住院时间。目前还没有经过验证的生物标志物用于快速诊断MIS-C。在这项研究中，我们使用光栅耦合荧光等离子体（GCFP）微阵列技术开发了美国和哥伦比亚MIS-C患者的儿科尿液和血清样本中的生物标志物特征。GCFP在夹心免疫测定中测量涂金衍射光栅传感器芯片上各个感兴趣区域（ROI）处的抗体-抗原相互作用，以基于样品中存在的分析物生成荧光信号。利用微阵列打印机，我们设计了第一代生物传感器芯片，能够从80个样品（唾液或血清）中捕获33种不同的分析物。在这里，我们在六个患者队列的唾液和血清样本中显示了潜在的生物标志物特征。在唾液样本中，我们注意到个别样本中芯片上偶尔出现的分析物离群值，并能够将这些样本与16 S RNA微生物组数据进行比较。这些比较表明这些患者口腔病原体相对丰度的差异。还对血清样本进行了免疫球蛋白同种型的微球免疫测定（MIA），结果显示MIS-C患者的几种COVID抗原特异性免疫球蛋白显著高于其他队列，从而确定了第二代生物传感器芯片的潜在新靶点。MIA还为我们的第二代芯片确定了其他生物标志物，验证了第一代芯片上生成的生物标志物签名，并帮助第二代芯片优化。有趣的是，来自美国的MIS-C样本比哥伦比亚样本具有更多样化和更强大的特征，这也在MIA细胞因子数据中得到了说明。这些观察结果确定了每个队列的新MIS-C生物标志物和生物标志物特征。最终，这些工具可能是一个潜在的诊断工具，用于快速识别MIS-C。
Multisystem inflammatory syndrome in children (MIS-C) is a rare but serious condition that can develop 4–6 weeks after a school age child becomes infected by SARS-CoV-2. To date, in the United States more than 8,862 cases of MIS-C have been identified and 72 deaths have occurred. This syndrome typically affects children between the ages of 5–13; 57% are Hispanic/Latino/Black/non-Hispanic, 61% of patients are males and 100% have either tested positive for SARS-CoV-2 or had direct contact with someone with COVID-19. Unfortunately, diagnosis of MIS-C is difficult, and delayed diagnosis can lead to cardiogenic shock, intensive care admission, and prolonged hospitalization. There is no validated biomarker for the rapid diagnosis of MIS-C. In this study, we used Grating-coupled Fluorescence Plasmonic (GCFP) microarray technology to develop biomarker signatures in pediatric salvia and serum samples from patients with MIS-C in the United States and Colombia. GCFP measures antibody-antigen interactions at individual regions of interest (ROIs) on a gold-coated diffraction grating sensor chip in a sandwich immunoassay to generate a fluorescent signal based on analyte presence within a sample. Using a microarray printer, we designed a first-generation biosensor chip with the capability of capturing 33 different analytes from 80 of sample (saliva or serum). Here, we show potential biomarker signatures in both saliva and serum samples in six patient cohorts. In saliva samples, we noted occasional analyte outliers on the chip within individual samples and were able to compare those samples to 16S RNA microbiome data. These comparisons indicate differences in relative abundance of oral pathogens within those patients. Microsphere Immunoassay (MIA) of immunoglobulin isotypes was also performed on serum samples and revealed MIS-C patients had several COVID antigen-specific immunoglobulins that were significantly higher than other cohorts, thus identifying potential new targets for the second-generation biosensor chip. MIA also identified additional biomarkers for our second-generation chip, verified biomarker signatures generated on the first-generation chip, and aided in second-generation chip optimization. Interestingly, MIS-C samples from the United States had a more diverse and robust signature than the Colombian samples, which was also illustrated in the MIA cytokine data. These observations identify new MIS-C biomarkers and biomarker signatures for each of the cohorts. Ultimately, these tools may represent a potential diagnostic tool for use in the rapid identification of MIS-C.
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DOI：
10.1002/0471140856.tx1816s53
发表时间：
2012-08
期刊：
Current protocols in toxicology
影响因子：
--
作者：
Molony, Ryan D;Rice, James M;Yuk, Jong Seol;Shetty, Vivek;Dey, Dipak;Lawrence, David A;Lynes, Michael A
通讯作者：
Lynes, Michael A
影响因子：
12.6
作者：
Rice, James M.;Stern, Lawrence J.;Guignon, Ernest F.;Lawrence, David A.;Lynes, Michael A.
通讯作者：
Lynes, Michael A.
影响因子：
4.5
作者：
Lee JH;Han HS;Lee JK
通讯作者：
Lee JK
DOI：
10.5114/aoms/144293
发表时间：
2022
期刊：
Archives of medical science : AMS
影响因子：
--
作者：
Qiu Z;Liu HH;Fan GZ;Chen WX;Hu P
通讯作者：
Hu P