Hubungan Kadar Delta Like Ligand 1 (DLL-1) Serum dan Cairan Serebrospinal (CSS) Terhadap Derajat Keparahan Meningitis Tuberkulosis
Bilah Samping Artikel
Isi Artikel Utama
Page: 1124-1131
Abstrak
Meningitis tuberkulosis (TBM) merupakan infeksi Mycobacterium Tuberculosis (M.Tb) pada selaput meningen dengan tingkat morbiditas yang tinggi. Prognosis TBM salah satunya ditentukan oleh derajat keparahan klinis berdasarkan klasifikasi British Medical Research Council (BMRC). Delta Like Ligand 1 (DLL-1) adalah protein transmembran yang berperan dalam pembentukan sel lemak (lipid) yang dibutuhkan M.tb untuk kelangsungan hidup, virulensi, dan pertahanan terhadap sistem imun inang. Ekspresi DLL-1 dapat terinduksi oleh stimulasi dinding sel M.tb terhadap respon imun manusia. Penelitian ini bertujuan untuk menganalisis hubungan antara kadar DLL-1 dalam serum dan cairan serebrospinal (CSS) dengan derajat keparahan klinis pasien TBM. Penelitian ini menggunakan desain potong lintang (cross-sectional) terhadap 30 pasien TBM yang menjalani pengobatan di RS M. Djamil Padang pada periode Oktober 2025 hingga Januari 2026. Kadar DLL-1 serum dan CSS diukur menggunakan metode enzyme-linked immunosorbent assay (ELISA), sedangkan derajat keparahan TBM dinilai berdasarkan kriteria BMRC. Analisis data dilakukan menggunakan SPSS versi 26.0 dengan tingkat signifikansi p< 0,05. Hasil analisis menunjukkan tidak terdapat perbedaan kadar DLL-1 serum (p = 0,129) dan kadar DLL-1 CSS terhadap derajat keparahan TBM (p = 0,097).
Unduhan
Rincian Artikel
Artikel ini berlisensiCreative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Referensi
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. DOI: 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. DOI: 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. DOI: 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. DOI: 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. DOI: 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. DOI: 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. DOI: 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. DOI: 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. DOI: 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. DOI: 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. DOI: 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. DOI: 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. DOI: 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. DOI: 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. DOI: 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. DOI: 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. DOI: 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. DOI: 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. DOI: 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. DOI: 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. DOI: 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. DOI: 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. DOI: 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. DOI: 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. DOI: 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. DOI: 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. DOI: 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. DOI: https://doi.org/10.3389/fcell.2020.534499