The potential value of Notch1 and DLL1 in the diagnosis and prognosis of patients with active TB

• Published in: Frontiers in immunology Vol. 14; p. 1134123
• Main Authors: Xie, Jinling, Chen, Yinzhong, Chen, Shihao, Long, Huaquan, Zhang, Weijian, Liu, Guoan
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 28.03.2023
• Subjects: active tuberculosis (TB); Biomarkers; DLL1 ligand; Humans; Immunology; Leukocytes, Mononuclear - metabolism; Notch1 receptor; Prognosis; Receptor, Notch1 - genetics; Receptor, Notch1 - metabolism; RNA, Messenger; ROC curve; Tuberculosis - diagnosis; Notch1 receptor; DLL1 ligand; active tuberculosis (TB); ROC curve; biomarkers
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2023.1134123

The Notch signaling pathway has been implicated in the pathogenesis of active tuberculosis (TB), and Th1-type cell-mediated immunity is essential for effective control of mycobacterial infection. However, it remains unclear whether Notch signaling molecules (Notch1, DLL1, and Hes1) and Th1-type factors (T-bet and IFN-γ) can serve as biomarkers for tracking the progression of active TB at different stages along with peripheral blood white blood cell (WBC) parameters. A total of 60 participants were enrolled in the study, including 37 confirmed TB patients (mild (n=17), moderate/severe (n=20)) and 23 healthy controls. The mRNA expression of Notch1, DLL1, Hes1, T-bet and IFN-γ in the peripheral blood mononuclear cells (PBMCs) of the subjects was measured by RT-qPCR, then analyzed for differences. Receiver Operating Characteristic curve (ROC) was used to assess the effectiveness of each factor as a biomarker in identifying lung injury. We found that mRNA expression levels of Notch1, DLL1, and Hes1 were upregulated in active TB patients, with higher levels observed in those with moderate/severe TB than those with mild TB or without TB. In contrast, mRNA levels of T-bet and IFN-γ were downregulated and significantly lower in mild and moderate/severe cases. Furthermore, the combiROC analysis of IFN-γ and the percentage of lymphocytes (L%) among WBC parameters showed superior discriminatory ability compared to other factors for identifying individuals with active TB versus healthy individuals. Notably, Notch pathway molecules were more effective than Th1-type factors and WBC parameters in differentiating mild and moderate/severe cases of active TB, particularly in the combiROC model that included Notch1 and Hes1. Our study demonstrated that Notch1, Hes1, IFN-γ, and L% can be used as biomarkers to identify different stages of active TB patients and to monitor the effectiveness of treatment.