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The emerging role of vitamin D binding protein in multiple sclerosis

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Abstract

Multiple sclerosis (MS) is the most common demyelinating disease of the central nervous system (CNS). A growing body of evidence supports a role for vitamin D in MS aetiology. Vitamin D binding protein (DBP) is the major plasma carrier of vitamin D metabolites and genetic differences in DBP gene have been found to influence vitamin D levels. We review here evidence supporting a role of DBP in MS. Several recent studies show that DBP levels in the cerebrospinal fluid correlate with MS course, being lower during relapses and higher in the secondary progressive phase. Further studies are needed to elucidate the potential use of DBP as a biological marker of MS course, but may be of use given the current lack of diagnostic tools for the prediction of MS development and progression.

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References

  1. Ahn J, Yu K, Stolzenberg-Solomon R, Simon KC, McCullough ML, Gallicchio L, Jacobs EJ, Ascherio A, Helzlsouer K, Jacobs KB, Li Q, Weinstein SJ, Purdue M, Virtamo J, Horst R, Wheeler W, Chanock S, Hunter DJ, Hayes RB, Kraft P, Albanes D (2010) Genome-wide association study of circulating vitamin D levels. Hum Mol Genet 19:2739–2745

    Article  PubMed  CAS  Google Scholar 

  2. Almeras L, Eyles D, Benech P, Laffite D, Villard C, Patatian A, Boucraut J, Mackay-Sim A, McGrath J, Feron F (2007) Developmental vitamin D deficiency alters brain protein expression in the adult rat: implications for neuropsychiatric disorders. Proteomics 7:769–780

    Article  PubMed  CAS  Google Scholar 

  3. Ascherio A, Munger KL, Simon KC (2010) Vitamin D and multiple sclerosis. Lancet Neurol 9:599–612

    Article  PubMed  Google Scholar 

  4. Bielekova B, Martin R (2004) Development of biomarkers in multiple sclerosis. Brain 127:1463–1478

    Article  PubMed  Google Scholar 

  5. Bouillon R, Van Assche FA, Van Baelen H, Heyns W, De Moor P (1981) Influence of the vitamin D-binding protein on the serum concentration of 1,25-dihydroxy vitamin D3. Significance of the free 1,25-dihydroxy vitamin D3 concentration. J Clin Invest 67:589–596

    Article  PubMed  CAS  Google Scholar 

  6. Chiasserini D, Di Filippo M, Candeliere A, Susta F, Orvietani PL, Calabresi P, Binaglia L, Sarchielli P (2008) CSF proteome analysis in multiple sclerosis patients by two-dimensional electrophoresis. Eur J Neurol 15:998–1001

    Article  PubMed  CAS  Google Scholar 

  7. Chun RF, Lauridsen AL, Suon L, Zella LA, Pike JW, Modlin RL, Martineau AR, Wilkinson RJ, Adams J, Hewison M (2010) Vitamin D-binding protein directs monocyte responses to 25-hydroxy- and 1,25-dihydroxyvitamin D. J Clin Endocrinol Metab 95(7):3368–3376

    Article  PubMed  CAS  Google Scholar 

  8. Comabella M, Fernandez M, Martin R, Rivera-Vallve S, Borras E, Chiva C, Julia E, Rovira A, Canto E, Alvarez-Cermeno JC, Villar LM, Tintore M, Montalban X (2010) Cerebrospinal fluid chitinase 3-like 1 levels are associated with conversion to multiple sclerosis. Brain 133:1082–1093

    Article  PubMed  Google Scholar 

  9. Cooke NE, Haddad JG (1989) Vitamin D binding protein (Gc-globulin). Endocr Rev 10:294–307

    Article  PubMed  CAS  Google Scholar 

  10. Correale J, Ysrraelit MC, Gaitan MI (2009) Immunomodulatory effects of Vitamin D in multiple sclerosis. Brain 132:1146–1160

    Article  PubMed  Google Scholar 

  11. Daiger SP, Schanfield MS, Cavalli-Sforza LL (1975) Group-specific component (Gc) proteins bind vitamin D and 25-hydroxyvitamin D. Proc Natl Acad Sci USA 72:2076–2080

    Article  PubMed  CAS  Google Scholar 

  12. Dick IM, Prince RL, Kelly JJ, Ho KK (1995) Oestrogen effects on calcitriol levels in post-menopausal women: a comparison of oral versus transdermal administration. Clin Endocrinol (Oxf) 43:219–224

    Article  CAS  Google Scholar 

  13. Dumont D, Noben JP, Raus J, Stinissen P, Robben J (2004) Proteomic analysis of cerebrospinal fluid from multiple sclerosis patients. Proteomics 4:2117–2124

    Article  PubMed  CAS  Google Scholar 

  14. Fernandes de Abreu DA, Eyles D, Feron F (2009) Vitamin D, a neuro-immunomodulator: implications for neurodegenerative and autoimmune diseases. Psychoneuroendocrinology 34(Suppl 1):S265–S277

    Article  PubMed  CAS  Google Scholar 

  15. Giovannoni G (2010) Cerebrospinal fluid neurofilament: the biomarker that will resuscitate the ‘Spinal Tap’. Mult Scler 16:285–286

    Article  PubMed  CAS  Google Scholar 

  16. Haddad JG, Fraser DR, Lawson DE (1981) Vitamin D plasma binding protein. Turnover and fate in the rabbit. J Clin Invest 67:1550–1560

    Article  PubMed  CAS  Google Scholar 

  17. Hammack BN, Fung KY, Hunsucker SW, Duncan MW, Burgoon MP, Owens GP, Gilden DH (2004) Proteomic analysis of multiple sclerosis cerebrospinal fluid. Mult Scler 10:245–260

    Article  PubMed  CAS  Google Scholar 

  18. Hayes CE, Cantorna MT, DeLuca HF (1997) Vitamin D and multiple sclerosis. Proc Soc Exp Biol Med 216:21–27

    PubMed  CAS  Google Scholar 

  19. Kamboh MI, Ferrell RE (1986) Ethnic variation in vitamin D-binding protein (GC): a review of isoelectric focusing studies in human populations. Hum Genet 72:281–293

    Article  PubMed  CAS  Google Scholar 

  20. Kew RR, Webster RO (1988) Gc-globulin (vitamin D-binding protein) enhances the neutrophil chemotactic activity of C5a and C5a des Arg. J Clin Invest 82:364–369

    Article  PubMed  CAS  Google Scholar 

  21. Klugmann M, Leichtlein CB, Symes CW, Klaussner BC, Brooks AI, Young D, During MJ (2006) A novel role of circadian transcription factor DBP in hippocampal plasticity. Mol Cell Neurosci 31:303–314

    Article  PubMed  CAS  Google Scholar 

  22. Kurtzke JF (1980) Geographic distribution of multiple sclerosis: an update with special reference to Europe and the Mediterranean region. Acta Neurol Scand 62:65–80

    Article  PubMed  CAS  Google Scholar 

  23. Lauridsen AL, Vestergaard P, Hermann AP, Brot C, Heickendorff L, Mosekilde L, Nexo E (2005) Plasma concentrations of 25-hydroxy-vitamin D and 1, 25-dihydroxy-vitamin D are related to the phenotype of Gc (vitamin D-binding protein): a cross-sectional study on 595 early postmenopausal women. Calcif Tissue Int 77:15–22

    Article  PubMed  CAS  Google Scholar 

  24. Lauridsen AL, Vestergaard P, Nexo E (2001) Mean serum concentration of vitamin D-binding protein (Gc globulin) is related to the Gc phenotype in women. Clin Chem 47:753–756

    PubMed  CAS  Google Scholar 

  25. Lehmensiek V, Sussmuth SD, Tauscher G, Brettschneider J, Felk S, Gillardon F, Tumani H (2007) Cerebrospinal fluid proteome profile in multiple sclerosis. Mult Scler 13:840–849

    Article  PubMed  CAS  Google Scholar 

  26. Liu S, Bai S, Qin Z, Yang Y, Cui Y, Qin Y (2009) Quantitative proteomic analysis of the cerebrospinal fluid of patients with multiple sclerosis. J Cell Mol Med 13:1586–1603

    Article  PubMed  CAS  Google Scholar 

  27. Mowry EM, Krupp LB, Milazzo M, Chabas D, Strober JB, Belman AL, McDonald JC, Oksenberg JR, Bacchetti P, Waubant E (2010) Vitamin D status is associated with relapse rate in pediatric-onset multiple sclerosis. Ann Neurol 67:618–624

    PubMed  CAS  Google Scholar 

  28. Munger KL, Levin LI, Hollis BW, Howard NS, Ascherio A (2006) Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA 296:2832–2838

    Article  PubMed  CAS  Google Scholar 

  29. Niino M, Kikuchi S, Fukazawa T, Yabe I, Tashiro K (2002) No association of vitamin D-binding protein gene polymorphisms in Japanese patients with MS. J Neuroimmunol 127:177–179

    Article  PubMed  CAS  Google Scholar 

  30. Noseworthy JH, Lucchinetti C, Rodriguez M, Weinshenker BG (2000) Multiple sclerosis. N Engl J Med 343:938–952

    Article  PubMed  CAS  Google Scholar 

  31. Ottervald J, Franzen B, Nilsson K, Andersson LI, Khademi M, Eriksson B, Kjellstrom S, Marko-Varga G, Vegvari A, Harris RA, Laurell T, Miliotis T, Matusevicius D, Salter H, Ferm M, Olsson T (2010) Multiple sclerosis: identification and clinical evaluation of novel CSF biomarkers. J Proteomics 73:1117–1132

    Article  PubMed  CAS  Google Scholar 

  32. Pugliatti M, Sotgiu S, Rosati G (2002) The worldwide prevalence of multiple sclerosis. Clin Neurol Neurosurg 104:182–191

    Article  PubMed  Google Scholar 

  33. Qin Z, Qin Y, Liu S (2009) Alteration of DBP levels in CSF of patients with MS by proteomics analysis. Cell Mol Neurobiol 29:203–210

    Article  PubMed  Google Scholar 

  34. Roussel BD, Macrez R, Jullienne A, Agin V, Maubert E, Dauphinot L, Potier MC, Plawinski L, Castel H, Hommet Y, Munuera J, Montaner J, Yepes M, Ali C, Vivien D (2009) Age and albumin D site-binding protein control tissue plasminogen activator levels: neurotoxic impact. Brain 132:2219–2230

    Article  PubMed  Google Scholar 

  35. Schneider GB, Benis KA, Flay NW, Ireland RA, Popoff SN (1995) Effects of vitamin D binding protein–macrophage activating factor (DBP-MAF) infusion on bone resorption in two osteopetrotic mutations. Bone 16:657–662

    Article  PubMed  CAS  Google Scholar 

  36. Sigmundsdottir H, Pan J, Debes GF, Alt C, Habtezion A, Soler D, Butcher EC (2007) DCs metabolize sunlight-induced vitamin D3 to ‘program’ T cell attraction to the epidermal chemokine CCL27. Nat Immunol 8:285–293

    Article  PubMed  CAS  Google Scholar 

  37. Sinotte M, Diorio C, Berube S, Pollak M, Brisson J (2009) Genetic polymorphisms of the vitamin D binding protein and plasma concentrations of 25-hydroxyvitamin D in premenopausal women. Am J Clin Nutr 89:634–640

    Article  PubMed  CAS  Google Scholar 

  38. Smolders J, Menheere P, Kessels A, Damoiseaux J, Hupperts R (2008) Association of vitamin D metabolite levels with relapse rate and disability in multiple sclerosis. Mult Scler 14:1220–1224

    Article  PubMed  CAS  Google Scholar 

  39. Speeckaert M, Huang G, Delanghe JR, Taes YE (2006) Biological and clinical aspects of the vitamin D binding protein (Gc-globulin) and its polymorphism. Clin Chim Acta 372:33–42

    Article  PubMed  CAS  Google Scholar 

  40. Steckley JL, Dyment DA, Sadovnick AD, Risch N, Hayes C, Ebers GC (2000) Genetic analysis of vitamin D related genes in Canadian multiple sclerosis patients. Canadian collaborative study group. Neurology 54:729–732

    PubMed  CAS  Google Scholar 

  41. Stoop MP, Dekker LJ, Titulaer MK, Lamers RJ, Burgers PC, Sillevis Smitt PA, van Gool AJ, Luider TM, Hintzen RQ (2009) Quantitative matrix-assisted laser desorption ionization-fourier transform ion cyclotron resonance (MALDI-FT-ICR) peptide profiling and identification of multiple-sclerosis-related proteins. J Proteome Res 8:1404–1414

    Article  PubMed  CAS  Google Scholar 

  42. Swamy N, Ghosh S, Schneider GB, Ray R (2001) Baculovirus-expressed vitamin D-binding protein–macrophage activating factor (DBP-maf) activates osteoclasts and binding of 25-hydroxyvitamin D(3) does not influence this activity. J Cell Biochem 81:535–546

    Article  PubMed  CAS  Google Scholar 

  43. Tremlett H, van der Mei IA, Pittas F, Blizzard L, Paley G, Mesaros D, Woodbaker R, Nunez M, Dwyer T, Taylor BV, Ponsonby AL (2008) Monthly ambient sunlight, infections and relapse rates in multiple sclerosis. Neuroepidemiology 31:271–279

    Article  PubMed  Google Scholar 

  44. Tumani H, Lehmensiek V, Rau D, Guttmann I, Tauscher G, Mogel H, Palm C, Hirt V, Suessmuth SD, Sapunova-Meier I, Ludolph AC, Brettschneider J (2009) CSF proteome analysis in clinically isolated syndrome (CIS): candidate markers for conversion to definite multiple sclerosis. Neurosci Lett 452:214–217

    Article  PubMed  CAS  Google Scholar 

  45. von Essen MR, Kongsbak M, Schjerling P, Olgaard K, Odum N, Geisler C (2010) Vitamin D controls T cell antigen receptor signaling and activation of human T cells. Nat Immunol 11:344–349

    Article  Google Scholar 

  46. Wang TJ, Zhang F, Richards JB, Kestenbaum B, van Meurs JB, Berry D, Kiel DP, Streeten EA, Ohlsson C, Koller DL, Peltonen L, Cooper JD, O’Reilly PF, Houston DK, Glazer NL, Vandenput L, Peacock M, Shi J, Rivadeneira F, McCarthy MI, Anneli P, de Boer IH, Mangino M, Kato B, Smyth DJ, Booth SL, Jacques PF, Burke GL, Goodarzi M, Cheung CL, Wolf M, Rice K, Goltzman D, Hidiroglou N, Ladouceur M, Wareham NJ, Hocking LJ, Hart D, Arden NK, Cooper C, Malik S, Fraser WD, Hartikainen AL, Zhai G, Macdonald HM, Forouhi NG, Loos RJ, Reid DM, Hakim A, Dennison E, Liu Y, Power C, Stevens HE, Jaana L, Vasan RS, Soranzo N, Bojunga J, Psaty BM, Lorentzon M, Foroud T, Harris TB, Hofman A, Jansson JO, Cauley JA, Uitterlinden AG, Gibson Q, Jarvelin MR, Karasik D, Siscovick DS, Econs MJ, Kritchevsky SB, Florez JC, Todd JA, Dupuis J, Hypponen E, Spector TD (2010) Common genetic determinants of vitamin D insufficiency: a genome-wide association study. Lancet 376:180–188

    Article  PubMed  CAS  Google Scholar 

  47. Xiao F, Chen D, Lu Y, Xiao Z, Guan LF, Yuan J, Wang L, Xi ZQ, Wang XF (2009) Proteomic analysis of cerebrospinal fluid from patients with idiopathic temporal lobe epilepsy. Brain Res 1255:180–189

    Article  PubMed  CAS  Google Scholar 

  48. Yamamoto N, Kumashiro R (1993) Conversion of vitamin D3 binding protein (group-specific component) to a macrophage activating factor by the stepwise action of beta-galactosidase of B cells and sialidase of T cells. J Immunol 151:2794–2802

    PubMed  CAS  Google Scholar 

  49. Zhang J, Kew RR (2004) Identification of a region in the vitamin D-binding protein that mediates its C5a chemotactic cofactor function. J Biol Chem 279:53282–53287

    Article  PubMed  CAS  Google Scholar 

  50. Zhang J, Sokal I, Peskind ER, Quinn JF, Jankovic J, Kenney C, Chung KA, Millard SP, Nutt JG, Montine TJ (2008) CSF multianalyte profile distinguishes Alzheimer and Parkinson diseases. Am J Clin Pathol 129:526–529

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Headington, Oxford, OX3 7BN, UK

    Giulio Disanto, Sreeram V. Ramagopalan, Andrea E. Para & Lahiru Handunnetthi

  2. Department of Clinical Neurology, The West Wing, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU, UK

    Giulio Disanto, Sreeram V. Ramagopalan, Andrea E. Para & Lahiru Handunnetthi

  3. Blizard Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, E1 2AT, UK

    Sreeram V. Ramagopalan

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  1. Giulio Disanto
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  2. Sreeram V. Ramagopalan
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  4. Lahiru Handunnetthi
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Correspondence to Lahiru Handunnetthi.

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Disanto, G., Ramagopalan, S.V., Para, A.E. et al. The emerging role of vitamin D binding protein in multiple sclerosis. J Neurol 258, 353–358 (2011). https://doi.org/10.1007/s00415-010-5797-8

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  • DOI: https://doi.org/10.1007/s00415-010-5797-8

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