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

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)15217-15226
Number of pages10
JournalAnalytical Chemistry
Volume95
Issue number41
DOIs
Publication statusPublished - 2023 Oct 17

All Science Journal Classification (ASJC) codes

  • Analytical Chemistry

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