Serum Matrix Metalloproteinase-9 Level and Previous Disease Activity in Relapsing-Remitting Multiple Sclerosis MMP-9 and Past-Year Activity in MS
International Clinical Neuroscience Journal,
Vol. 10 No. 1 (2023),
15 January 2023
,
Page e5
https://doi.org/10.22037/icnj.v10i1.38610
Abstract
Background: Matrix metalloproteinase-9 (MMP-9) is a marker of blood-brain barrier destruction, that is elevated during clinical relapses in multiple sclerosis (MS). In between relapses, MMP-9 levels decline but remain higher than the normal population. This study aimed to investigate the relation between serum MMP-9 level and disease activity in MS during relapse-free periods.
Methods: This was a retrospective study conducted on adult patients with relapsing-remitting MS (RRMS) whose last relapse was ≥ 1 month ago. Serum MMP-9 was withdrawn at the time of recruitment and correlated with parameters of disease activity.
Results: Of the 40 patients recruited, 75% were women. The mean age was 36.2 ± 8.4 years, and the mean disease duration was 7 years. Patients’ median Expanded Disability Status Scale (EDSS) was 3.5 (IQR: 2.5-5.25), the median duration since the last relapse was 3 months, and the median duration since last corticosteroid administration was 6 months. On multivariate regression analysis, there was a significant association between serum MMP-9 levels and duration since the last relapse (B: -0.004, 95% CI: -0.007- -0.002, P = 0.001) as well as duration since the last corticosteroid intake (B: -0.003, 95% CI: -0.006- -0.001, P = 0.005).
Conclusion: Serum MMP-9 levels correlated with the duration since last relapse and duration since last corticosteroids administration during relapse-free periods.
- Disease activity, Multiple sclerosis, Serum matrix metalloproteinase 9, Relapse
How to Cite
References
Bigaut K, Cohen M, Durand-Dubief F, Maillart E, Planque E, Zephir H, et al. How to switch disease-modifying treatments in multiple sclerosis: guidelines from the French Multiple Sclerosis Society (SFSEP). Mult Scler Relat Disord. 2021;53:103076. doi: 10.1016/j.msard.2021.103076.
Miller AE. Switching or discontinuing disease-modifying therapies for multiple sclerosis. Continuum (Minneap Minn).
;22(3):851-63. doi: 10.1212/con.0000000000000327 .
Corboy JR, Weinshenker BG, Wingerchuk DM. Comment on 2018 American Academy of Neurology guidelines on disease-modifying therapies in MS. Neurology. 2018;90(24):1106-12. doi: 10.1212/wnl.0000000000005574.
Fox EJ, Havrdova E. Breakthrough disease in multiple sclerosis–the problem and treatment options. Eur Neurol Rev. 2013;7(Suppl 2):24-31. doi: 10.17925/enr.2013.08.s1.24 .
Merwick A, Sweeney BJ. Functional symptoms in clinically definite MS--pseudo-relapse syndrome. Int MS J. 2008;15(2):47-51.
Mills EA, Mirza A, Mao-Draayer Y. Emerging approaches for validating and managing multiple sclerosis relapse. Front Neurol. 2017;8:116. doi: 10.3389/fneur.2017.00116 .
Radbruch A. Are some agents less likely to deposit gadolinium in the brain? Magn Reson Imaging. 2016;34(10):1351-4. doi: 10.1016/j.mri.2016.09.001.
Graber JJ, Dhib-Jalbut S. Biomarkers of disease activity in multiple sclerosis. J Neurol Sci. 2011;305(1-2):1-10. doi: 10.1016/j.jns.2011.03.026.
Huang J, Khademi M, Fugger L, Lindhe Ö, Novakova L, Axelsson M, et al. Inflammation-related plasma and CSF biomarkers for multiple sclerosis. Proc Natl Acad Sci U S A. 2020;117(23):12952-60. doi: 10.1073/pnas.1912839117.
Rempe RG, Hartz AMS, Bauer B. Matrix metalloproteinases in the brain and blood-brain barrier: versatile breakers and makers. J Cereb Blood Flow Metab. 2016;36(9):1481-507. doi: 10.1177/0271678x16655551.
Mirshafiey A, Asghari B, Ghalamfarsa G, Jadidi-Niaragh F, Azizi G. The significance of matrix metalloproteinases in the immunopathogenesis and treatment of multiple sclerosis. Sultan Qaboos Univ Med J. 2014;14(1):e13-25. doi: 10.12816/0003332.
Toft-Hansen H, Nuttall RK, Edwards DR, Owens T. Key metalloproteinases are expressed by specific cell types in experimental autoimmune encephalomyelitis. J Immunol. 2004;173(8):5209-18. doi: 10.4049/jimmunol.173.8.5209.
Trentini A, Castellazzi M, Cervellati C, Manfrinato MC, Tamborino C, Hanau S, et al. Interplay between matrix metalloproteinase-9, matrix metalloproteinase-2, and interleukins in multiple sclerosis patients. Dis Markers. 2016;2016:3672353. doi: 10.1155/2016/3672353.
Voloshyna N, Vasylovskyy V, Nehreba T, Chernenko M, Vovk V. Matrix metalloproteinase-9 and inflammation in different types of multiple sclerosis. EUREKA: Health Sciences. 2016;1:39-44. doi: 10.21303/2504-5679.2016.00039.
Benešová Y, Vašků A, Novotná H, Litzman J, Štourač P, Beránek M, et al. Matrix metalloproteinase-9 and matrix metalloproteinase-2 as biomarkers of various courses in multiple sclerosis. Mult Scler. 2009;15(3):316-22. doi: 10.1177/1352458508099482.
Aktas O, Wattjes MP, Stangel M, Hartung HP. [Diagnosis of multiple sclerosis: revision of the McDonald criteria 2017]. Nervenarzt. 2018;89(12):1344-54. doi: 10.1007/s00115- 018-0550-0. [German].
Snitker S, Xie K, Ryan KA, Yu D, Shuldiner AR, Mitchell BD, et al. Correlation of circulating MMP-9 with white blood cell count in humans: effect of smoking. PLoS One. 2013;8(6):e66277. doi: 10.1371/journal.pone.0066277.
Kieseier BC, Kiefer R, Clements JM, Miller K, Wells GM, Schweitzer T, et al. Matrix metalloproteinase-9 and -7 are regulated in experimental autoimmune encephalomyelitis. Brain. 1998;121(Pt 1):159-66. doi: 10.1093/brain/121.1.159.
CLOUD-CLONE CORP (CCC). ELISA Kit for Matrix Metalloproteinase 9 (MMP9) | SEA553Hu | Homo sapiens (Human) CLOUD-CLONE CORP (CCC). http://www. cloud-clone.com/products/SEA553Hu.html. Accessed October 1, 2021.
BioVendor. Human Matrix Metalloproteinase-9 Elisa. https:// www.biovendor.com/file/6762/PDS_HuMMP9_ELISA_ ENG_001.pdf. Accessed August 6, 2021.
Konstantinou GN. Enzyme-linked immunosorbent assay (ELISA). In: Lin J, Alcocer M, eds. Food Allergens: Methods and Protocols. Vol 1592. New York, NY: Springer; 2017. p. 79-94. doi: 10.1007/978-1-4939-6925-8_7.
Sormani MP, De Stefano N. Defining and scoring response to IFN-β in multiple sclerosis. Nat Rev Neurol. 2013;9(9):504- 12. doi: 10.1038/nrneurol.2013.146.
Matrix metalloproteinase 9 as a marker of disease activity in multiple sclerosis. Nat Clin Pract Neurol. 2006;2(9):464. doi: 10.1038/ncpneuro0231 .
Harris VK, Tuddenham JF, Sadiq SA. Biomarkers of multiple sclerosis: current findings. Degener Neurol Neuromuscul Dis. 2017;7:19-29. doi: 10.2147/dnnd.s98936.
Bucova M, Majernikova B, Durmanova V, Cudrakova D, Gmitterova K, Lisa I, et al. HMGB1 as a potential new marker of disease activity in patients with multiple sclerosis. Neurol Sci. 2020;41(3):599-604. doi: 10.1007/s10072-019-04136-3.
Håkansson I. Biomarkers and Disease Activity in Multiple Sclerosis: A Cohort Study on Patients with Clinically Isolated Syndrome and Relapsing Remitting Multiple Sclerosis. Linköping University Electronic Press; 2019.
Bittner S, Oh J, Havrdová EK, Tintoré M, Zipp F. The potential of serum neurofilament as biomarker for multiple sclerosis. Brain. 2021;144(10):2954-63. doi: 10.1093/brain/awab241.
Novakova L, Zetterberg H, Sundström P, Axelsson M, Khademi M, Gunnarsson M, et al. Monitoring disease activity in multiple sclerosis using serum neurofilament light protein. Neurology. 2017;89(22):2230-7. doi: 10.1212/wnl.0000000000004683.
Latronico T, Liuzzi GM. Metalloproteinases and their inhibitors as therapeutic targets for multiple sclerosis: current evidence and future perspectives. Metalloproteinases Med. 2017;4:1-13. doi: 10.2147/mnm.s88655.
Castellazzi M, Ligi D, Contaldi E, Quartana D, Fonderico M, Borgatti L, et al. Multiplex matrix metalloproteinases analysis in the cerebrospinal fluid reveals potential specific patterns in multiple sclerosis patients. Front Neurol. 2018;9:1080. doi: 10.3389/fneur.2018.01080.
Amini R, Karampoor S, Zahednasab H, Keyvani H, Gheiasian M, Azizi Jalilian F. Serum levels of matrix metalloproteinase-2, -9, and vitamin D in patients with multiple sclerosis with or without herpesvirus-6 seropositivity. Braz J Infect Dis. 2020;24(2):144-9. doi: 10.1016/j.bjid.2020.02.001.
Fainardi E, Castellazzi M, Bellini T, Manfrinato MC, Baldi E, Casetta I, et al. Cerebrospinal fluid and serum levels and intrathecal production of active matrix metalloproteinase-9 (MMP-9) as markers of disease activity in patients with multiple sclerosis. Mult Scler. 2006;12(3):294-301. doi: 10.1191/135248506ms1274oa.
Yılmaz U, Gücüyener K, Gürkaş E, Demir E, Serdaroğlu A, Atak A, et al. Matrix metalloproteinase-7, matrix metalloproteinase-9, and disease activity in pediatric multiple sclerosis. Pediatr Neurol. 2013;48(3):255-6. doi: 10.1016/j. pediatrneurol.2012.12.003.
Trentini A, Manfrinato MC, Castellazzi M, Tamborino C, Roversi G, Volta CA, et al. TIMP-1 resistant matrix metalloproteinase-9 is the predominant serum active isoform associated with MRI activity in patients with multiple sclerosis. Mult Scler. 2015;21(9):1121-30. doi: 10.1177/1352458514560925.
Romi F, Helgeland G, Gilhus NE. Serum levels of matrix metalloproteinases: implications in clinical neurology. Eur Neurol. 2012;67(2):121-8. doi: 10.1159/000334862.
Avolio C, Ruggieri M, Giuliani F, Liuzzi GM, Leante R, Riccio P, et al. Serum MMP-2 and MMP-9 are elevated in different multiple sclerosis subtypes. J Neuroimmunol. 2003;136(1- 2):46-53. doi: 10.1016/s0165-5728(03)00006-7.
ICH GCP. ICH GCP (Good Clinical Practice) Training Course. https://ichgcp.net/. Published 2011. Accessed April 4, 2020.
HHS. Federalwide Assurance (FWA) for the Protection of Human Subjects | HHS.gov. https://www.hhs.gov/ohrp/ register-irbs-and-obtain-fwas/fwas/fwa-protection-of-human-subjecct/index.html. Accessed August 6, 2021.
- Abstract Viewed: 201 times
- PDF Downloaded: 274 times