Lambda-free light chain: A serum marker of dengue disease via NS3 protease-mediated antibody cleavage
ABSTRACTDengue poses a significant global public health threat, with diverse clinical manifestations due to complex interactions between the host and the pathogen. Recent reports have highlighted elevated serum-free light chain (FLC) levels in viral infectious diseases. Hence, our study aimed to inv...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2023-12-01
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| Series: | Virulence |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/21505594.2023.2279355 |
| _version_ | 1797367196691726336 |
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| author | Sheng-Hsuan Wang Bai-Jiun Kuo Tzu-Chuan Ho Shu-Wen Wan Ko-Lun Yen Po-Hui Huang Oscar Guey Chuen Perng Po-Lin Chen Yu-Wen Chien Yu-Chih Lo |
| author_facet | Sheng-Hsuan Wang Bai-Jiun Kuo Tzu-Chuan Ho Shu-Wen Wan Ko-Lun Yen Po-Hui Huang Oscar Guey Chuen Perng Po-Lin Chen Yu-Wen Chien Yu-Chih Lo |
| author_sort | Sheng-Hsuan Wang |
| collection | DOAJ |
| description | ABSTRACTDengue poses a significant global public health threat, with diverse clinical manifestations due to complex interactions between the host and the pathogen. Recent reports have highlighted elevated serum-free light chain (FLC) levels in viral infectious diseases. Hence, our study aimed to investigate serum FLC levels in dengue patients. The findings revealed elevated serum λ FLCs, which were associated with the severity of dengue. Receiver operating characteristic curve (ROC) analysis demonstrated that λ FLCs may serve as a serum marker for identifying dengue disease (AUC: 0.7825, sensitivity: 80, specificity: 71.43) and classifying severe dengue (AUC: 0.8102, sensitivity: 75, specificity: 79.52). The viral protease, Dengue virus (DENV) nonstructural protein 3 (NS3), acts as a protease that cleaves viral polyproteins as well as host substrates. Therefore, we proposed that antibodies might be potential targets of NS3 protease, leading to an increase in FLCs. LC/MS-MS analysis confirmed that λ FLCs were the predominant products after antibody degradation by NS3 protease. Additionally, purified NS3 protease cleaved both human IgG and DENV2-neutralizing antibodies, resulting in the presence of λ FLCs. Moreover, NS3 protease administration in vitro led to a reduction in the neutralizing efficacy of DENV2-neutralizing antibodies. In summary, the elevated serum λ FLC levels effectively differentiate dengue patients from healthy individuals and identify severe dengue. Furthermore, the elevation of serum λ FLCs is, at least in part, mediated through NS3 protease-mediated antibody cleavage. These findings provide new insights for developing diagnostic tools and understanding the pathogenesis of DENV infection. |
| first_indexed | 2024-03-08T17:13:48Z |
| format | Article |
| id | doaj.art-5e7b1c4805354a1194ecf9a2e39a6435 |
| institution | Directory Open Access Journal |
| issn | 2150-5594 2150-5608 |
| language | English |
| last_indexed | 2024-03-08T17:13:48Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Virulence |
| spelling | doaj.art-5e7b1c4805354a1194ecf9a2e39a64352024-01-03T17:26:57ZengTaylor & Francis GroupVirulence2150-55942150-56082023-12-0114110.1080/21505594.2023.2279355Lambda-free light chain: A serum marker of dengue disease via NS3 protease-mediated antibody cleavageSheng-Hsuan Wang0Bai-Jiun Kuo1Tzu-Chuan Ho2Shu-Wen Wan3Ko-Lun Yen4Po-Hui Huang5Oscar Guey Chuen Perng6Po-Lin Chen7Yu-Wen Chien8Yu-Chih Lo9Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, TaiwanDepartment of Biotechnology and Bioindustry Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, TaiwanInstitute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, TaiwanDepartment of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, TaiwanInstitute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, TaiwanDepartment of Biotechnology and Bioindustry Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, TaiwanInstitute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, TaiwanDepartment of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, TaiwanDepartment of Public Health, College of Medicine, National Cheng Kung University, Tainan, TaiwanDepartment of Biotechnology and Bioindustry Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, TaiwanABSTRACTDengue poses a significant global public health threat, with diverse clinical manifestations due to complex interactions between the host and the pathogen. Recent reports have highlighted elevated serum-free light chain (FLC) levels in viral infectious diseases. Hence, our study aimed to investigate serum FLC levels in dengue patients. The findings revealed elevated serum λ FLCs, which were associated with the severity of dengue. Receiver operating characteristic curve (ROC) analysis demonstrated that λ FLCs may serve as a serum marker for identifying dengue disease (AUC: 0.7825, sensitivity: 80, specificity: 71.43) and classifying severe dengue (AUC: 0.8102, sensitivity: 75, specificity: 79.52). The viral protease, Dengue virus (DENV) nonstructural protein 3 (NS3), acts as a protease that cleaves viral polyproteins as well as host substrates. Therefore, we proposed that antibodies might be potential targets of NS3 protease, leading to an increase in FLCs. LC/MS-MS analysis confirmed that λ FLCs were the predominant products after antibody degradation by NS3 protease. Additionally, purified NS3 protease cleaved both human IgG and DENV2-neutralizing antibodies, resulting in the presence of λ FLCs. Moreover, NS3 protease administration in vitro led to a reduction in the neutralizing efficacy of DENV2-neutralizing antibodies. In summary, the elevated serum λ FLC levels effectively differentiate dengue patients from healthy individuals and identify severe dengue. Furthermore, the elevation of serum λ FLCs is, at least in part, mediated through NS3 protease-mediated antibody cleavage. These findings provide new insights for developing diagnostic tools and understanding the pathogenesis of DENV infection.https://www.tandfonline.com/doi/10.1080/21505594.2023.2279355Dengue virusλ light chainserum markerDENV proteaseNS2B-NS3proNS3pro |
| spellingShingle | Sheng-Hsuan Wang Bai-Jiun Kuo Tzu-Chuan Ho Shu-Wen Wan Ko-Lun Yen Po-Hui Huang Oscar Guey Chuen Perng Po-Lin Chen Yu-Wen Chien Yu-Chih Lo Lambda-free light chain: A serum marker of dengue disease via NS3 protease-mediated antibody cleavage Virulence Dengue virus λ light chain serum marker DENV protease NS2B-NS3pro NS3pro |
| title | Lambda-free light chain: A serum marker of dengue disease via NS3 protease-mediated antibody cleavage |
| title_full | Lambda-free light chain: A serum marker of dengue disease via NS3 protease-mediated antibody cleavage |
| title_fullStr | Lambda-free light chain: A serum marker of dengue disease via NS3 protease-mediated antibody cleavage |
| title_full_unstemmed | Lambda-free light chain: A serum marker of dengue disease via NS3 protease-mediated antibody cleavage |
| title_short | Lambda-free light chain: A serum marker of dengue disease via NS3 protease-mediated antibody cleavage |
| title_sort | lambda free light chain a serum marker of dengue disease via ns3 protease mediated antibody cleavage |
| topic | Dengue virus λ light chain serum marker DENV protease NS2B-NS3pro NS3pro |
| url | https://www.tandfonline.com/doi/10.1080/21505594.2023.2279355 |
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