Relationship Between Delta Like Ligand 1 (DLL-1) Levels in Serum and Cerebrospinal Fluid (CSF) with The Severity of Tuberculosis Meningitis
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Abstract
Tuberculous meningitis (TBM) is an infection caused by Mycobacterium tuberculosis (M.tb) affecting the meninges, characterized by high morbidity rates. The prognosis of TBM is partially determined by clinical severity, classified according to the British Medical Research Council (BMRC) scale. Delta Like Ligand 1 (DLL-1) is a transmembrane protein that plays a role in the formation of lipid cells, which are essential for the survival, virulence, and defense of M.tb against the host immune system. DLL-1 expression can be induced by the stimulation of M.tb cell walls in response to the human immune system. This study aims to analyze the correlation between DLL-1 levels in the serum and cerebrospinal fluid (CSF) with the clinical severity of TBM patients. A cross-sectional study was conducted involving 30 TBM patients treated at M. Djamil Central General Hospital, Padang, from October 2025 to January 2026. Serum and CSF DLL-1 levels were measured using the enzyme-linked immunosorbent assay (ELISA) method, while TBM severity was assessed based on the BMRC criteria. Data analysis was performed using SPSS version 26.0 with a significance level of p < 0.05. The results of the analysis showed no significant difference in serum DLL-1 levels (p = 0.129) or CSS DLL-1 levels in relation to the severity of TBM (p = 0.097).
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References
WHO. Tuberculosis 2026.
Thakur K, Das M, Dooley K, Gupta A. The Global Neurological Burden of Tuberculosis. Semin Neurol 2018;38:226–37. https://doi.org/10.1055/s-0038-1651500.
Donovan J, Figaji A, Imran D, Phu NH, Rohlwink U, Thwaites GE. The neurocritical care of tuberculous meningitis. Lancet Neurol 2019;18:771–83. https://doi.org/10.1016/S1474-4422(19)30154-1.
Christie D, Rashid H, El-Bashir H, Sweeney F, Shore T, Booy R, et al. Impact of meningitis on intelligence and development: A systematic review and meta-analysis. PLoS One 2017;12:e0175024. https://doi.org/10.1371/journal.pone.0175024.
Peng T, Zhou Y, Li J, Li J, Wan W, Jia Y. Detection of Delta-like 1 ligand for the diagnosis of tuberculous meningitis: An effective and rapid diagnostic method. Journal of International Medical Research 2014;42:728–36. https://doi.org/10.1177/0300060513498669.
Slane VH, Tobin EH, Unakal CG. Tuberculous Meningitis. 2024.
Tiara A., Salim H., Winugroho W. Buku Ajar Neurologi Klinis Edisi Kedua. vol. 2. Kedua. Jakarta: Yayasan Otak Sehat Indonesia; 2022.
Soria J, Metcalf T, Mori N, Newby RE, Montano SM, Huaroto L, et al. Mortality in hospitalized patients with tuberculous meningitis. BMC Infect Dis 2019;19:9. https://doi.org/10.1186/s12879-018-3633-4.
Thwaites G. Tuberculous meningitis. Medicine 2017;45:670–3. https://doi.org/10.1016/j.mpmed.2017.08.010.
Guo C, Liu K-W, Tong J, Gao M-Q. Prevalence and prognostic significance of malnutrition risk in patients with tuberculous meningitis. Front Public Health 2025;12. https://doi.org/10.3389/fpubh.2024.1391821.
Bansal-Mutalik R, Nikaido H. Mycobacterial outer membrane is a lipid bilayer and the inner membrane is unusually rich in diacyl phosphatidylinositol dimannosides. Proceedings of the National Academy of Sciences 2014;111:4958–63. https://doi.org/10.1073/pnas.1403078111.
Hildebrand D, Uhle F, Sahin D, Krauser U, Weigand MA, Heeg K. The Interplay of Notch Signaling and STAT3 in TLR-Activated Human Primary Monocytes. Front Cell Infect Microbiol 2018;8. https://doi.org/10.3389/fcimb.2018.00241.
Oo N, K D. Epidemiology, Pathogenesis, Clinical Manifestations, and Management Strategies of Tuberculous Meningitis. Archives of Internal Medicine Research 2025:48–58. https://doi.org/10.26502/aimr.0195.
Bahr NC, Tugume L, Rajasingham R, Kiggundu R, Williams DA, Morawski B, et al. Improved diagnostic sensitivity for tuberculous meningitis with Xpert<SUP>®</SUP> MTB/RIF of centrifuged CSF. The International Journal of Tuberculosis and Lung Disease 2015;19:1209–15. https://doi.org/10.5588/ijtld.15.0253.
PENG Yue, JIA Yanjie, Wang Cuiqin, Zhang Gangyu, Peng Tao. The clinical value of cerebrospinal fluid of Notch1 of DLL1 detection of infectious diseases of the central nervous system. Life Sci J 2013:1503–7.
Bahr NC, Nuwagira E, Evans EE, Cresswell F V, Bystrom P V, Byamukama A, et al. Diagnostic accuracy of Xpert MTB/RIF Ultra for tuberculous meningitis in HIV-infected adults: a prospective cohort study. Lancet Infect Dis 2018;18:68–75. https://doi.org/10.1016/S1473-3099(17)30474-7.
Xie J, Chen Y, Chen S, Long H, Zhang W, Liu G. The potential value of Notch1 and DLL1 in the diagnosis and prognosis of patients with active TB. Front Immunol 2023;14. https://doi.org/10.3389/fimmu.2023.1134123.
Li J, Li J, Jia Y. Levels of soluble delta-like ligand 1 in the serum and cerebrospinal fluid of tuberculous meningitis patients. Neural Regen Res 2012;7:874–8. https://doi.org/10.3969/j.issn.1673-5374.2012.11.013.
M. Sopiyudin Dahlan. Statistik untuk Kedokteran dan Kesehatan . 5th ed. Jakarta: Buku Kompas; 2013.
WHO. Global Tuberculosis Report 2022.
Peer V, Schwartz N, Green MS. Gender differences in tuberculosis incidence rates—A pooled analysis of data from seven high-income countries by age group and time period. Front Public Health 2023;10. https://doi.org/10.3389/fpubh.2022.997025.
Dodd PJ, Osman M, Cresswell F V., Stadelman AM, Lan NH, Thuong NTT, et al. The global burden of tuberculous meningitis in adults: A modelling study. PLOS Global Public Health 2021;1:e0000069. https://doi.org/10.1371/journal.pgph.0000069.
Gupta M, Srikrishna G, Klein SL, Bishai WR. Genetic and hormonal mechanisms underlying sex-specific immune responses in tuberculosis. Trends Immunol 2022;43:640–56. https://doi.org/10.1016/j.it.2022.06.004.
Horton KC, MacPherson P, Houben RMGJ, White RG, Corbett EL. Sex Differences in Tuberculosis Burden and Notifications in Low- and Middle-Income Countries: A Systematic Review and Meta-analysis. PLoS Med 2016;13:e1002119. https://doi.org/10.1371/journal.pmed.1002119.
He H, Xu J, Peng Q, Li Y, Huang Y, Zhang Y-L, et al. The application value of cerebrospinal fluid immunoglobulin in tuberculous meningitis. Microbiol Spectr 2024;12. https://doi.org/10.1128/spectrum.00157-24.
Chandrasekaran P, Saravanan N, Bethunaickan R, Tripathy S. Malnutrition: Modulator of Immune Responses in Tuberculosis. Front Immunol 2017;8. https://doi.org/10.3389/fimmu.2017.01316.
Franco JV, Bongaerts B, Metzendorf M-I, Risso A, Guo Y, Peña Silva L, et al. Undernutrition as a risk factor for tuberculosis disease. Cochrane Database of Systematic Reviews 2024;2025. https://doi.org/10.1002/14651858.CD015890.pub2.
CDC. Tuberculosis Risk Factors 2024.
Dharmana SN, Singla N, Sharma K, Modi M, Goyal M. Prevalence of Seizures in Patients With Tuberculous Meningitis (TBM) and Their Clinical Outcomes. Cureus 2025. https://doi.org/10.7759/cureus.77210.
Davis AG, Rohlwink UK, Proust A, Figaji AA, Wilkinson RJ. The pathogenesis of tuberculous meningitis. J Leukoc Biol 2019;105:267–80. https://doi.org/10.1002/JLB.MR0318-102R.
Mondiani YQ, Iryawati D, Munir B. Non-Specific Headache as the Main Manifestation of Tuberculous Meningitis: A Rare Case Report. MNJ (Malang Neurology Journal) 2025;11:241–6. https://doi.org/10.21776/ub.mnj.2025.011.02.15.
DLL1 protein expression summary. The Human Protein Atlas 2021.
Delta-like canonical Notch ligand 1” (DLL1). Uniprot 2025.
Jahantigh D, Salimi S, Alavi-Naini R, Emamdadi A, Owaysee Osquee H, Farajian Mashhadi F. Association between TLR4 and TLR9 gene polymorphisms with development of pulmonary tuberculosis in Zahedan, southeastern Iran. ScientificWorldJournal 2013;2013:534053. https://doi.org/10.1155/2013/534053.
De Nardo D. Toll-like receptors: Activation, signalling and transcriptional modulation. Cytokine 2015;74:181–9. https://doi.org/10.1016/j.cyto.2015.02.025.
Mizuhara E, Nakatani T, Minaki Y, Sakamoto Y, Ono Y, Takai Y. MAGI1 Recruits Dll1 to Cadherin-based Adherens Junctions and Stabilizes It on the Cell Surface. Journal of Biological Chemistry 2005;280:26499–507. https://doi.org/10.1074/jbc.M500375200.
Zanotti S, Yu J, Adhikari S, Canalis E. Glucocorticoids inhibit notch target gene expression in osteoblasts. J Cell Biochem 2018;119:6016–23. https://doi.org/10.1002/jcb.26798.
Rossini M, Martini F, Torreggiani E, Fortini F, Aquila G, Sega FVD, et al. Metformin Induces Apoptosis and Inhibits Notch1 in Malignant Pleural Mesothelioma Cells. Front Cell Dev Biol 2021;8. https://doi.org/10.3389/fcell.2020.534499.