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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Greaves, Ronda / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter


IMPACT FACTOR 2018: 3.638

CiteScore 2018: 2.44

SCImago Journal Rank (SJR) 2018: 1.191
Source Normalized Impact per Paper (SNIP) 2018: 1.205

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1437-4331
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Volume 53, Issue 5

Issues

Uric acid: a potential biomarker of multiple sclerosis and of its disability

Marcello Moccia
  • Multiple Sclerosis Centre, Department of Neuroscience, Reproductive Science and Odontostomatology, Federico II University of Naples, Naples, Italy
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/ Roberta Lanzillo
  • Corresponding author
  • Multiple Sclerosis Centre, Department of Neuroscience, Reproductive Science and Odontostomatology, Federico II University of Naples, Naples, Italy
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/ Raffaele Palladino
  • Department of Public Health, Federico II University of Naples, Naples, Italy
  • Department of Primary Care and Public Health, Imperial College, London, UK
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/ Cinzia Russo
  • Multiple Sclerosis Centre, Department of Neuroscience, Reproductive Science and Odontostomatology, Federico II University of Naples, Naples, Italy
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/ Antonio Carotenuto
  • Multiple Sclerosis Centre, Department of Neuroscience, Reproductive Science and Odontostomatology, Federico II University of Naples, Naples, Italy
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/ Marco Massarelli
  • Multiple Sclerosis Centre, Department of Neuroscience, Reproductive Science and Odontostomatology, Federico II University of Naples, Naples, Italy
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/ Giovanni Vacca
  • Multiple Sclerosis Centre, Department of Neuroscience, Reproductive Science and Odontostomatology, Federico II University of Naples, Naples, Italy
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/ Veria Vacchiano
  • Multiple Sclerosis Centre, Department of Neuroscience, Reproductive Science and Odontostomatology, Federico II University of Naples, Naples, Italy
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/ Antonio Nardone / Maria Triassi / Vincenzo Brescia Morra
  • Multiple Sclerosis Centre, Department of Neuroscience, Reproductive Science and Odontostomatology, Federico II University of Naples, Naples, Italy
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Published Online: 2014-09-20 | DOI: https://doi.org/10.1515/cclm-2014-0744

Abstract

Background: Uric acid (UA) is a strong natural scavenger of reactive oxygen and nitrogen species, with evidence of possible use in the treatment of animal models of multiple sclerosis (MS). Consequently, serum UA has gained much attention as a possible biomarker of MS. We aim to investigate differences in serum UA levels between MS subjects and controls and evaluate possible relationships of UA with MS clinical features.

Methods: We recruited relapsing-remitting and secondary progressive MS subjects and healthy controls and measured their serum UA levels. We excluded subjects presenting concomitant conditions affecting UA levels.

Results: MS subjects (n=362) and controls (n=181) were recruited by propensity score matching (PSM). Statistical analyses were corrected for age, gender, and renal function. MS subjects presented significantly lower serum UA levels than controls (analysis of variance, p=0.014, adjusted r2=0.3036). Linear regression analysis showed a relationship between UA levels and disease duration (p<0.001, adjusted r2=0.3158, coefficient –0.00039), time from diagnosis (p<0.001, adjusted r2=0.3100, coefficient –0.0012), and Expanded Disability Status Scale (EDSS) (p<0.001, adjusted r2=0.3230, coefficient –0.1).

Conclusions: Our findings support the importance of serum UA as a biomarker of MS disability and progression. Further studies with longitudinal design should be specifically designed to evaluate the importance of UA in the different stages of MS and in relation to distinct therapeutic strategies.

Keywords: biomarker; Expanded Disability Status Scale (EDSS); multiple sclerosis; oxidant; scavenger; urate; uric acid

References

  • 1.

    Smith JK, Kapoor R, Felts PA. Demyelination: the role reactive oxygen nitrogen species. Brain Pathol 1991;9:69–92.Google Scholar

  • 2.

    Schreibelt G, van Horssen J, van Rossum S, Dijkstra CD, Drukarch B, de Vries HE. Therapeutic potential and biological role of endogenous antioxidant enzymes in multiple sclerosis pathology. Brain Res Rev 2007;56:322–30.CrossrefPubMedWeb of ScienceGoogle Scholar

  • 3.

    Hooper DC, Bagasra O, Marini JC, Zborek A, Ohnishi ST, Kean R, et al. Prevention of experimental allergic encephalomyelitis by targeting nitric oxide and peroxynitrite: implications for the treatment of multiple sclerosis. Proc Natl Acad Sci USA 1997;94:2528–33.CrossrefGoogle Scholar

  • 4.

    Hooper DC, Scott GS, Zborek A, Mikheeva T, Kean RB, Koprovski H, et al. Uric acid A peroxynitrite scavenger inhibits CNS inflammation blood-CNS barrier permeability changes and tissue damage in mouse model of multiple sclerosis. FASEB J 2000;14:691–8.PubMedGoogle Scholar

  • 5.

    Squadrito GL, Cueto R, Splenser AE, Valavanidis A, Zhang H, Uppu RM, et al. Reaction of uric acid with peroxinitrite and implications for the mechanism of neuroprotection by uric acid. Arch Biochem Biophys 2000;376:333–7.CrossrefGoogle Scholar

  • 6.

    Scott GS, Spitsin SV, Kean RB, Mikheeva T, Koprowski H, Hooper DC. Therapeutic intervention in experimental allergic encephalomyelitis by administration of uric acid precursors. Proc Natl Acad Sci USA 2002;99:16303–8.CrossrefGoogle Scholar

  • 7.

    Hooper DC, Spitsin S, Kean RB, Champio JM, Dickson GM, Chaudhry I, et al. Uric acid, a natural scavenger of peroxynitrite, in experimental allergic encephalomyelitis and multiple sclerosis. Proc Natl Acad Sci USA 1998;95:675–80.CrossrefGoogle Scholar

  • 8.

    Toncev G, Milicic B, Toncev S, Samardzic G. Serum uric acid levels in multiple sclerosis patients correlate with activity of disease and blood-brain barrier dysfunction. Eur J Neurol 2002;9:221–6.PubMedCrossrefGoogle Scholar

  • 9.

    Dujmovic I, Pekmezovic T, Obrenovic R, Nicolić A, Spasic M, Mostarica Stojkovic M, et al. Cerebrospinal fluid and serum uric acid levels in patients with multiple sclerosis. Clin Chem Lab Med 2009;47:848–53.PubMedGoogle Scholar

  • 10.

    Spitsin S, Hooper DC, Mikheeva T, Koprowski H. Uric acid levels in patients with multiple sclerosis: analysis in mono- and dizygotic twins. Mult Scler 2001;7:165–6.CrossrefPubMedGoogle Scholar

  • 11.

    Sotgiu S, Pugliatti M, Sanna A, Sotgiu A, Fois ML, Arru G, et al. Serum uric acid and multiple sclerosis. Neurol Sci 2002; 23:183–8.CrossrefPubMedGoogle Scholar

  • 12.

    Peng F, Zhang B, Zhong X, Li J, Xu G, Hu X, et al. Serum uric acid levels of patients with multiple sclerosis and other neurological diseases. Mult Scler 2008;14:188–96.PubMedGoogle Scholar

  • 13.

    Ashtari F, Bahar M, Aghaei M, Zahed A. Serum uric acid level in patients with relapsing-remitting multiple sclerosis. J Clin Neurosci 2013;20:676–8.PubMedCrossrefGoogle Scholar

  • 14.

    Drulović J, Dujmović I, Stojsavljević N, Mesaros S, Andjelković S, Miljković D, et al. Uric acid levels in sera from patients with multiple sclerosis. J Neurol 2001;248:121–6.PubMedGoogle Scholar

  • 15.

    Knapp CM, Constantinescu CS, Tan JH, McLean R, Cherryman GR, Gottlob I. Serum uric acid levels in optic neuritis. Mult Scler 2004;10:278–80.PubMedCrossrefGoogle Scholar

  • 16.

    Liu B, Shen Y, Xiao K, Tang Y, Cen L, Wei J. Serum uric acid levels in patients with multiple sclerosis: a meta-analysis. Neurol Res 2012;34:163–71.Web of SciencePubMedGoogle Scholar

  • 17.

    Guerrero AL, Gutiérrez F, Iglesias F, Martín-Polo J, Merino S, Martín-Serradilla JI, et al. Serum uric acid levels in multiple sclerosis patients inversely correlate with disability. Neurol Sci 2011;32:347–50.Web of ScienceCrossrefPubMedGoogle Scholar

  • 18.

    Ljubisavljevic S, Stojanovic I, Vojinovic S, Vojinovic S, Dunjic O, Stojanov D, et al. Association of serum bilirubin and uric acid levels changes during neuroinflammation in patients with initial and relapsed demyelination attacks. Metab Brain Dis 2013;28:629–38.PubMedWeb of ScienceCrossrefGoogle Scholar

  • 19.

    Constantinescu CS, Freitag P, Kappos L. Increase in serum levels of uric acid, an endogenous antioxidant, under treatment with glatiramer acetate for multiple sclerosis. Mult Scler 2000;6:378–81.PubMedCrossrefGoogle Scholar

  • 20.

    Toncev G, Milicic B, Toncev S, Samardzic G. High-dose methylprednisolone therapy in multiple sclerosis increases serum uric acid levels. Clin Chem Lab Med 2002;40:505–8.PubMedGoogle Scholar

  • 21.

    Koprowsky H, Spitsin S, Hooper C. Prospects for the treatment of multiple sclerosis by raising serum levels of uric acid, a scavenger of peroxinitrite. Ann Neurol 2001;49:139.CrossrefGoogle Scholar

  • 22.

    Gonsette RE, Sindic C, D’hooghe MB, De Deyn PP, Medaer R, Michotte A, et al. Boosting endogenous neuroprotection in multiple sclerosis: the Association of Inosine and Interferon beta in relapsing-remitting Multiple Sclerosis (ASIIMS) trial. Mult Scler 2010;16:455–62.CrossrefWeb of ScienceGoogle Scholar

  • 23.

    Spitsin S, Hooper DC, Leist T, Streletz LJ, Mikheeva T, Koprowskil H. Inactivation of peroxynitrite in multiple sclerosis patients after oral administration of inosine may suggest possible approaches to therapy of the disease. Mult Scler 2001;7:313–9.CrossrefPubMedGoogle Scholar

  • 24.

    Mostert JP, Ramsaransing GS, Heersema DJ, Heerings M, Wilczak N, De Keyer J. Serum uric acid levels and leukocyte nitric oxide production in multiple sclerosis patients outside relapses. J Neurol Sci 2005;231:41–4.Google Scholar

  • 25.

    Ramsaransing GS, Heersema DJ, De Keyser J. Serum uric acid, dehydroepiandrosterone sulphate, and apolipoprotein E genotype in benign vs. progressive multiple sclerosis. Eur J Neurol 2005;12:514–8.CrossrefPubMedGoogle Scholar

  • 26.

    Massa J, O’Reilly E, Munger KL, Delorenze GN, Ascherio A. Serum uric acid and risk of multiple sclerosis. J Neurol 2009;256:1643–8.PubMedCrossrefGoogle Scholar

  • 27.

    Zoccolella S, Tortorella C, Iaffaldano P, Direnzo V, D’Onghia M, Luciannatelli E, et al. Low serum urate levels are associated to female gender in multiple sclerosis patients. PLoS One 2012;7:e40608.PubMedGoogle Scholar

  • 28.

    Amorini AM, Petzold A, Tavazzi B, Eikelenboom J, Keir G, Belli A, et al. Increase of uric acid and purine compounds in biological fluids of multiple sclerosis patients. Clin Biochem 2009;42:1001–6.Web of ScienceCrossrefPubMedGoogle Scholar

  • 29.

    Salemi G, Gueli MC, Vitale F, Battaglieri F, Guglielmini E, Ragonese P, et al. Blood lipids, homocysteine, stress factors, and vitamins in clinically stable multiple sclerosis patients. Lipids Health Dis 2010;9:19.PubMedWeb of ScienceCrossrefGoogle Scholar

  • 30.

    Tavazzi B, Batocchi AP, Amorini AM, Nociti V, Dúrso S, Longo S, et al. Serum metabolic profile in multiple sclerosis patients. Mult Scler Int 2011;2011:167156.PubMedGoogle Scholar

  • 31.

    Koch M, De Keyser J. Uric acid in multiple sclerosis. Neurol Res 2006;28:316–9.CrossrefPubMedGoogle Scholar

  • 32.

    Moccia M, Picillo M, Erro R, Vitale C, Longo K, Amboni M, et al. Is serum uric acid related to non-motor symptoms in de-novo Parkinson’s disease patients? Parkinsonism Relat Disord 2014;20:772–5.CrossrefPubMedGoogle Scholar

  • 33.

    Poser CM, Paty DW, Scheinberg L, McDonald WI, Davis FA, Ebers GC, et al. New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol 1983; 13:227–31.PubMedCrossrefGoogle Scholar

  • 34.

    McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol 2001;50:121–7.CrossrefPubMedGoogle Scholar

  • 35.

    Lublin FD, Reingold SC. Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. Neurology 1996;46:907–11.CrossrefGoogle Scholar

  • 36.

    Bowman GL, Shannon J, Frei B, Kaye JA, Quinn JF. Uric acid as a CNS antioxidant. J Alzheimers Dis 2010;19:1331–6.PubMedWeb of ScienceGoogle Scholar

  • 37.

    Niklasson F, Hetta J, Degrell I. Hypoxanthine, xanthine, urate and creatinine concentration gradients in cerebrospinal fluid. Ups J Med Sci 1988;93:225–32.CrossrefPubMedGoogle Scholar

About the article

Corresponding author: Roberta Lanzillo, Multiple Sclerosis Centre, Department of Neuroscience, Reproductive Science and Odontostomatology, Federico II University of Naples, Via Pansini 5, 80131 Naples, Italy, Phone: +390817463764, Fax: +390815463663, E-mail: ;


Received: 2014-07-18

Accepted: 2014-08-28

Published Online: 2014-09-20

Published in Print: 2015-04-01


Citation Information: Clinical Chemistry and Laboratory Medicine (CCLM), Volume 53, Issue 5, Pages 753–759, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm-2014-0744.

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