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Lambda-free light chain: A serum marker of dengue disease via NS3 protease-mediated antibody cleavage
- Source :
- Virulence, Vol 14, Iss 1 (2023)
- Publication Year :
- 2023
- Publisher :
- Taylor & Francis Group, 2023.
-
Abstract
- 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.
Details
- Language :
- English
- ISSN :
- 21505594 and 21505608
- Volume :
- 14
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- Virulence
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.5e7b1c4805354a1194ecf9a2e39a6435
- Document Type :
- article
- Full Text :
- https://doi.org/10.1080/21505594.2023.2279355