Assessment of Serum Interleukin 40 and 41 Levels in Patients with Multiple Sclerosis
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Abstract
Multiple sclerosis (MS) is a chronic immune-mediated disease characterized by inflammation, demyelination, gliosis, and neurodegeneration in the central nervous system (CNS). Interleukin 40 and 41 are novel immune-modulatory cytokines associated with inflammatory and autoimmune diseases. The study aims to evaluate novel cytokines in MS patients and their role as a potential biomarker for JCV reactivation in MS patients. Five millilitres of blood were taken from 165 individuals (age range 18–53 years), divided into 109 samples from MS patients (37 males and 72 females) who enrolled at Dr. Saad AlWitry Hospital for Neurosciences in Baghdad and 56 healthy volunteers (18 males and 38 females). The patients were distributed into three groups: MS patients, JCV-associated MS patients, and MS patients without therapy. ELISA has been used to measure the cytokine levels in the blood of MS patients and healthy volunteers. The serum level mean of IL-40 decreased significantly (p ≤ 0.001) in the three groups of patients: MS patients (20.005±1.346 ng/ml), JCV-associated MS patients (24.520±1.454 ng/ml), and MS patients without therapy (24.686±3.008 ng/ml) compared to controls (42.287±4.742 ng/ml). For IL-41, its mean level also decreased significantly (p ≤ 0.001) in MS patients (1.397±0.224 ng/ml), JCV-associated MS patients (1.545±0.175 ng/ml), and MS patients without therapy (1.161±0.276 ng/ml) compared to controls (3.044±0.321 ng/ml). Newly discovered cytokines (IL-40 and IL-41) were negatively associated with the severity of the disease and may have a role as a potential biomarker for MS.
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References
Abed, R. M., Abdulmalek, H. W., Yaaqoob, L. A., Altaee, M. F., & Kamona, Z. K. (2023). Serum level and genetic polymorphism of IL-38 and IL-40 in autoimmune thyroid disease. Iraqi Journal of Science, 2786-2797. https://doi.org/10.24996/ijs.2023.64.6.12
Al Rubaye, A. M., Sharquie, I. K., & Gorial, F. I. (2023). Serum interleukin 40: An innovative diagnostic biomarker for patients with systemic lupus erythematosus. The Medical Journal of Malaysia, 78(5), 609-615.
Arthur, R. R., & Shah, K. V. (1989). Occurrence and significance of papovaviruses BK and JC in the urine. Progress in Medical Virology, 36, 42-61.
Bani-Wais, D. F., & Ad'hiah, A. H. (2023). A novel intergenic variant, rs2004339 A/G, of the gene encoding interleukin-40, C17orf99, is associated with risk of rheumatoid arthritis in Iraqi women. Molecular Immunology, 164, 39-46. https://doi.org/10.1016/j.molimm.2023.11.002
Branco, L. P., Adoni, T., Apostolos-Pereira, S. L., Brooks, J. B. B., Correa, E. C., Damasceno, C. A., Eboni, A. C. B., Fezer, L., Gama, P. D. D., Goncalves, M. V. M., & Gomes, S. (2018). Serological profile of John Cunningham virus (JCV) in patients with multiple sclerosis. Arquivos de Neuro-Psiquiatria, 76, 588-591. https://doi.org/10.1590/0004-282X20180083
Bridgewood, C., Russell, T., Weedon, H., Baboolal, T., Watad, A., Sharif, K., Cuthbert, R., Wittmann, M., Wechalekar, M., & McGonagle, D. (2019). The novel cytokine Metrnl/IL-41 is elevated in psoriatic arthritis synovium and inducible from both entheseal and synovial fibroblasts. Clinical Immunology, 208, 108253. https://doi.org/10.1016/j.clim.2019.108253
Bsteh, G., Ehling, R., Lutterotti, A., Hegen, H., Di Pauli, F., Auer, M., Deisenhammer, F., Reindl, M., & Berger, T. (2016). Long-term clinical prognostic factors in relapsing-remitting multiple sclerosis: Insights from a 10-year observational study. PLoS ONE, 11(7), e0158978. https://doi.org/10.1371/journal.pone.0158978
Catalan-Dibene, J., McIntyre, L. L., & Zlotnik, A. (2018). Interleukin 30 to interleukin 40. Journal of Interferon & Cytokine Research, 38(10), 423-439. https://doi.org/10.1089/jir.2018.0089
Dabbagh-Gorjani, F. (2024). A comprehensive review on the role of interleukin‐40 as a biomarker for diagnosing inflammatory diseases. Autoimmune Diseases, 2024(1), 3968767. https://doi.org/10.1155/2024/3968767
Dennison, L., Brown, M., Kirby, S., & Galea, I. (2018). Do people with multiple sclerosis want to know their prognosis? A UK nationwide study. PLoS ONE, 13(2), e0193407. https://doi.org/10.1371/journal.pone.0193407
Gloudina, M. H., Mogamat, S. H., Rajiv, T. E., & Tandi, M. (2012). The haematological profile of patients with multiple sclerosis. Open Journal of Modern Neurosurgery, 2012.
Gong, L., Zhou, Y., Shi, S., Ying, L., Li, Y., & Li, M. (2023). Increased serum IL-41 is associated with disease activity in rheumatoid arthritis. Clinica Chimica Acta, 538, 169-174. https://doi.org/10.1016/j.cca.2022.11.021
Hussein, R. K., Al-Obaidi, A. B., & Hussein, M. R. (2023). Prevalence of Anti JC Polyomavirus IgG in a sample of Iraqi kidney transplant recipients and healthy blood donors. Iraqi Journal of Medical Sciences, 21(2).
Lassmann, H. (2005). Mechanisms of multiple sclerosis. Drug Delivery Today: Disease Mechanisms/Nervous System, 2(4), 448-452. https://doi.org/10.1016/j.ddmec.2005.11.007
Najafi, P., Hadizadeh, M., Cheong, J. P. G., Mohafez, H., & Abdullah, S. (2022). Cytokine profile in patients with multiple sclerosis following exercise: A systematic review of randomized clinical trials. International Journal of Environmental Research and Public Health, 19(13), 8151. https://doi.org/10.3390/ijerph19138151
Navrátilová, A., Bečvář, V., Hulejová, H., Tomčík, M., Štolová, L., Mann, H., Růžičková, O., Šléglová, O., Závada, J., Pavelka, K., & Vencovský, J. (2023). New pro-inflammatory cytokine IL-40 is produced by activated neutrophils and plays a role in the early stages of seropositive rheumatoid arthritis. RMD Open, 9(2), e002894. https://doi.org/10.1136/rmdopen-2022-002894
Nociti, V., & Romozzi, M. (2022). Multiple sclerosis and autoimmune comorbidities. Journal of Personalized Medicine, 12(11), 1828.
Rommer, P., Zettl, U., Kieseier, B., Hartung, H., Menge, T., & Frohman, E. (2014). Requirement for safety monitoring for approved multiple sclerosis therapies: An overview. Clinical & Experimental Immunology, 175(3), 397-407. https://doi.org/10.1111/cei.12206
Schneider, E. M., & Dörries, K. (1993). High frequency of polyomavirus infection in lymphoid cell preparations after allogeneic bone marrow transplantation. Transplantation Proceedings, 25(1 Pt 2), 1271-1273.
Severa, M., Rizzo, F., Giacomini, E., Salvetti, M., & Coccia, E. M. (2015). IFN-β and multiple sclerosis: Cross-talking of immune cells and integration of immunoregulatory networks. Cytokine & Growth Factor Reviews, 26(2), 229-239. https://doi.org/10.1016/j.cytogfr.2014.11.005
Shi, R., He, M., Peng, Y., & Xia, X. (2024). Homotherapy for heteropathy: Interleukin‐41 and its biological functions. Immunology. https://doi.org/10.1111/imm.13791
Stamatellos, V. P., & Papazisis, G. (2023). Safety and monitoring of the treatment with disease-modifying therapies (DMTs) for multiple sclerosis (MS). Current Reviews in Clinical and Experimental Pharmacology, 18(1), 39-50. https://doi.org/10.2174/2772432817666220412110720
Titus, H. E., Chen, Y., Podojil, J. R., Robinson, A. P., Balabanov, R., Popko, B., & Miller, S. D. (2020). Pre-clinical and clinical implications of “inside-out” vs. “outside-in” paradigms in multiple sclerosis etiopathogenesis. Frontiers in Cellular Neuroscience, 14, 599717. https://doi.org/10.3389/fncel.2020.599717
Wijburg, M. T., Kleerekooper, I., Lissenberg-Witte, B. I., de Vos, M., Warnke, C., Uitdehaag, B. M. J., Barkhof, F., Killestein, J., & Wattjes, M. P. (2018). Association of progressive multifocal leukoencephalopathy lesion volume with JC virus polymerase chain reaction results in cerebrospinal fluid of natalizumab-treated patients with multiple sclerosis. JAMA Neurology, 75(7), 827-833. https://doi.org/10.1001/jamaneurol.2018.0094