Antibody Profiling of Dengue Severities Using Flavivirus Protein Microarrays

Pei Shan Tsai, Pin Xian Du, Batuhan Birol Keskin, Nan Yao Lee, Shu Wen Wan, Ya Lan Lin, Wen Yu Su, Pei Chun Lin, Wei Hsun Lin, Hsi Chang Shih, Tzong Shiann Ho, Guan Da Syu

研究成果: Article同行評審

摘要

Dengue is a viral disease transmitted by Aedes aegypti mosquitoes. According to the World Health Organization, about half of the world’s population is at risk of dengue. There are four serotypes of the dengue virus. After infection with one serotype, it will be immune to such a serotype. However, subsequent infection with other serotypes will increase the risk of severe outcomes, e.g., dengue hemorrhagic fever, dengue shock syndrome, and even death. Since severe dengue is challenging to predict and lacks molecular markers, we aim to build a multiplexed Flavivirus protein microarray (Flaviarray) that includes all of the common Flaviviruses to profile the humoral immunity and cross-reactivity in the dengue patients with different outcomes. The Flaviarrays we fabricated contained 17 Flavivirus antigens with high reproducibility (R-square = 0.96) and low detection limits (172-214 pg). We collected serums from healthy subjects (n = 36) and dengue patients within 7 days after symptom onset (mild dengue (n = 21), hospitalized nonsevere dengue (n = 29), and severe dengue (n = 36)). After profiling the serum antibodies using Flaviarrays, we found that patients with severe dengue showed higher IgG levels against multiple Flavivirus antigens. With logistic regression, we found groups of markers with high performance in distinguishing dengue patients from healthy controls as well as hospitalized from mild cases (AUC > 0.9). We further reported some single markers that were suitable to separate dengue patients from healthy controls (AUC > 0.9) and hospitalized from mild outcomes (AUC > 0.8). Together, Flaviarray is a valuable tool to profile antibody specificities, uncover novel markers for decision-making, and shed some light on early preventions and treatments.

原文English
頁(從 - 到)15217-15226
頁數10
期刊Analytical Chemistry
95
發行號41
DOIs
出版狀態Published - 2023 10月 17

All Science Journal Classification (ASJC) codes

  • 分析化學

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