Low Serum Myeloperoxidase Levels in Multiple Sclerosis Patients

Abstract

Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system characterized by inflammation, demyelination, and neurodegeneration. It may lead to physical disability, acute neurological, and cognitive problems. The specific etiology of MS has not been clearly defined to date. One of the key factors that play a role in the pathogenesis of MS is oxidative stress, which increases inflammation and neurodegeneration. Myeloperoxidase (MPO) is one of the enzymes secreted by activated inflammatory cells and is produced by monocytes, macrophages, microglia, and neutrophils. At the same time, myeloperoxidase is one of the components of oxidative stress. MPO has been investigated many times in MS patients, but peripheral blood levels of MPO have been studied very few times. This study investigated serum MPO levels in MS, and the relationship of these levels with patients' age, disease duration, prognosis, annualized relapse rate (ARR), EDSS scores, and disease-modifying drug therapies (DMT) used. The study included 50 MS patients and 50 healthy controls, and their demographic and clinical characteristics were determined. Serum MPO levels were significantly lower in MS patients than in the healthy control group (p=0034). No significant correlation was found between MPO levels and patients' age, EDSS scores, disease year, DMTs used, and disease progression (p>0.05). These results show that low MPO levels in MS patients have an important role in the pathogenesis of MS. There is a need for further studies on this subject.

Keywords

• Multiple sclerosis
• myeloperoxidase
• oxidative stress

References

1. 1. Bjelobaba I, Savic D, and Lavrnja I. Multiple sclerosis and neuroinflammation: the overview of current and prospective therapies. Current Pharmaceutical Design 2017; 23(5): 693–730.
2. 2. Hayes CE, Donald Acheson E. A unifying multiple sclerosis etiology linking virus infection, sunlight, and vitamin D, through viral interleukin-10. Med Hypotheses 2008;71(1):85–90.
3. 3. Calabresi PA. Diagnosis and management of multiple sclerosis. Am Fam Physician 2004; 70(10):1935–1944.
4. 4. Sadovnick AD, Ebers GC. Epidemiology of multiple sclerosis: a critical overview. Can J Neurol Sci 1993; 20(1):17–29.
5. 5. Lublin FD, Reingold SC. Defining the clinical course of multiple sclerosis: Results of an international survey. Neurology 1996; 46: 907–911.
6. 6. Dutta R, Trapp BD. Relapsing and progressive forms of multiple sclerosis—Insights from pathology. Curr Opin Neurol 2014; 27: 271–278.
7. 7. Bendszus M, Storch-Hagenlocher B. Multiple sclerosis, and other demyelinating diseases. In Inflammatory Diseases of the Brain. Hähnel S, Ed: Springer: Berlin/Heidelberg, Germany; 2013, 3–18.
8. 8. Bradley PP, Christensen RD, Rothstein G. Cellular and extracellular myeloperoxidase in pyogenic inflammation. Blood 1982; 60 (3): 618–622.

9. 9. Hoy A, Leininger-Muller B, Kutter D, et al. Growing significance of myeloperoxidase in non-infectious diseases. Clin Chem Lab Med 2002; 40: 2–8.
10. 10. Heinecke JW. Tyrosyl radical production by myeloperoxidase: a phagocyte pathway for lipid peroxidation and dityrosine cross-linking of proteins. Toxicology 2002; 177 (1): 11– 22.
11. 11. Zhang R, Brennan ML, Shen Z, et al. Myeloperoxidase functions as a major enzymatic catalyst for initiation of lipid peroxidation at sites of inflammation. J Biol Chem 2002; 277(48): 46116–46122.
12. 12. Gray E, Thomas TL, Betmouni S, Scolding N, Love S. Elevated myeloperoxidase activity in white matter in multiple sclerosis. Neurosci Lett 2008; 444(2): 195–198
13. 13. Nagra RM, Becher B, Tourtellotte WW, et al. Immunohistochemical and genetic evidence of myeloperoxidase involvement in multiple sclerosis. J Neuroimmunol 1997;78(1-2): 97–107.
14. 14. Brennan M, Gaur A, Pahuja A, Lusis AJ, Reynolds WF. Mice lacking myeloperoxidase are more susceptible to experimental autoimmune encephalomyelitis. J Neuroimmunol 2001; 112: 97–105
15. 15. Bradly PP, Priebat DA, Christensen RD, Rothstein G. Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker. J ınvest Dermatol. 1982; 78: 206-220
16. 16. Goldenberg MM. Multiple sclerosis review. P T 2012; 37: 175–184.
17. 17. Miller, E. Multiple sclerosis. Adv. Exp. Med. Biol. 2012; 724: 222–238.
18. 18. Bendszus M, Storch-Hagenlocher B. Multiple sclerosis and other demyelinating diseases. In Inflammatory Diseases of the Brain; Hähnel S, Ed.; Springer: Berlin/Heidelberg, Germany, 2013; 3–18
19. 19. Lee DH, Gold R, Linker RA. Mechanisms of oxidative damage in multiple sclerosis and neurodegenerative diseases: Therapeutic modulation via fumaric acid esters. Int. J. Mol. Sci. 2012; 13: 11783–11803.
20. 20. Gilgun-Sherki Y, Melamed E, Offen D. The role of oxidative stress in the pathogenesis of multiple sclerosis: The need for effective antioxidant therapy. J. Neurol. 2004; 251: 261–268.
21. 21. Van Horssen J, Witte ME, Schreibelt G, deVries HE. Radical changes in multiple sclerosis pathogen-esis. Biochim. Biophys. Acta 2011; 1812: 141–150.
22. 22. Adamczyk B, Wawrzyniak S, Kasperczyk S, Adamczyk-Sowa M. The Evaluation of Oxidative Stress Parameters in Serum Patients with Relapsing-Remitting Multiple Sclerosis Treated with II-Line Immunomodulatory Therapy. Oxidative Medicine and Cellular Longevity Volume. 2017; 12
23. 23.Ray RS, Katyal A. Myeloperoxidase: Bridging the gap in neurodegeneration. Neurosci. Biobehav. Rev. 2016; 68: 611–620.
24. 24.Kuokkanen S, Gschwend M, Rioux JD, et al. Genomewide scan of multiple sclerosis in Finnish multiplex families. Am J Hum Genet 1997; 61: 1379–87.
25. 25. Sawcer S, Jones HB, Feakes R, et al. A genome screen in multiple sclerosis reveals susceptibility loci on chromosome 6p21 and 17q22. Nat Genet 1996; 13: 464–468.
26. 26. Gray E, Thomas TL, Betmouni S, Scolding N, Love S. Elevated activity and microglial expression of myeloperoxidase in demyelinated cerebral cortex in multiple sclerosis. Brain Pathol. 2008a; 18 (1): 86-95.
27. 27.Forghani R, Wojtkiewicz GR, Zhang Y, Seeburg D, Bautz BR, Pulli B et al. Demyelinating diseases: myeloperoxidase as an imaging biomarker and therapeutic target. Radiology. 2012; 263(2): 451-460.
28. 28. Chen JW, Breckwoldt MO, Aikawa E, Chiang G, Weissleder R. Myeloperoxidasetargeted imaging of active inflammatory lesions in murine experimental autoimmune encephalomyelitis. Brain. 2008; 131: 1123-1133.
29. 29. Sajad M, Zargan J, Chawla R, Umar S, Sadaqat M, Khan HA. Hippocampal neurodegeneration in experimental autoimmune encephalomyelitis (EAE): potential role of inflammation activated myeloperoxidase. Mol Cell Biochem. 2009; 328(1- 2):183-188.
30. 30. Pulli B, Bure L, Wojtkiewicz GR, Iwamoto Y, Ali M, Li D. Multiple sclerosis: myeloperoxidase immunoradiology improves detection of acute and chronic disease in experimental model. Radiology. 2015; 275(2): 480-489
31. 31. Nusshold C, Kollroser M, Kofeler H, Rechberger G, Reicher H, Ullen A. Hypochlorite modification of sphingomyelin generates chlorinated lipid species that induce apoptosis and proteome alterations in dopaminergic PC12 neurons in vitro. Free Radic Biol Med. 2010; 48(12): 1588-1600.
32. 32. G Ramsaransing, A Teelken, V M Prokopenko, AV Arutjunyan, J De Keyser. Low leucocyte myeloperoxidase activity in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry 2003; 74: 953–955
33. 33. Tasset I, Bahamonde C, Agüera E, Conde C, Cruz AH, Pérez-Herrera A. Effect of natalizumab on oxidative damage biomarkers in relapsing-remitting multiple sclerosis. Pharmacological Reports 2013; 65: 624-631