Advertisement

Lipids in Multiple Sclerosis

  • L. Rinaldi
  • F. Grassivaro
  • P. Gallo
Reference work entry

Abstract:

Increasing evidence suggests that lipids antigens may be target of autoimmune attacks in inflammatory diseases of the central nervous system. Preliminary observations in multiple sclerosis and in experimental autoimmune encephalomyelitis indicate that both T cell and antibody reactivity to structural lipids of myelin may play a role in determining autoimmune-mediated demyelination. Molecular mimicry between bacterial and myelin glycolipids has been observed, and a subset of NKT cells specific for glycolipid antigens has been identified. Increased sulfatide-reactive T-cells and antibodies were demonstrated in multiple sclerosis patients. The possibility that myelin lipids may be targets for autoimmune reactions in central nervous system diseases opens new research and therapeutic perspectives for multiple sclerosis.

Keywords

Multiple Sclerosis Experimental Autoimmune Encephalomyelitis Multiple Sclerosis Patient iNKT Cell Oligodendrocyte Progenitor Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

List of Abbreviations:

(APC)

antigen presenting cells

(EAE)

experimental autoimmune encephalomyelitis

(IFN)

interferon

(LPA)

lysophosphatidic acid

(MHC-I)

major histocompatibility complex class I

[MBP]

myelin basic protein

[MOG]

myelin oligodendrocyte protein

(NOD)

non-obese diabetic

(OPC)

oligodendrocyte progenitor cell

[PLP]

proteolipid protein

(TCR)

T cell receptor

(TNF)

tumor necrosis factor

References

  1. Alling C, Vanier MT, Svennerholm L 1971. Lipid alterations in apparently normal white matter in multiple sclerosis. Brain Res 35(2): 325–336.PubMedCrossRefGoogle Scholar
  2. Anliker B and Chun J 2004a. Cell surface receptors in lysophospholipid signaling. Semin Cell Dev Biol 15: 457–465.PubMedCrossRefGoogle Scholar
  3. Anliker B and Chun J 2004b. Lysophospholipid G protein-coupled receptors. J Biol Chem 279: 20555–20558.PubMedCrossRefGoogle Scholar
  4. Bansal AS, Abdul-Karim B, Malik RA, Goulding P, Pumphrey RS, et al. 1994. Igm ganglioside GM1 antibodies in patients with autoimmune disease or neuropathy, and controls. J Clin Pathol 47: 300–302.PubMedCrossRefGoogle Scholar
  5. Battistini L, Fischer FR, Raine CS, Brosnan CF 1996. CD1b is expressed in multiple sclerosis lesions. J Neuroimmunol 67: 145–151.PubMedGoogle Scholar
  6. Bendelac A, Bonneville M, Kearney JF 2001. Autoreactivity by design: Innate B and T lymphocytes. Nat Rev Immunol 1: 177–186.PubMedCrossRefGoogle Scholar
  7. Bendelac A, Rivera MN, Park SH, Roark JH 1997. Mouse CD1-specific NK1 T cells: Development, specificity, and function. Annu Rev Immunol 15: 535–562.PubMedCrossRefGoogle Scholar
  8. Bendelac A, Savage PB, Luc T 2007. The biology of NKT cells. Annu Rev Immunol 25: 297–336.PubMedCrossRefGoogle Scholar
  9. Ben-Menacem G, Kubler-Kielb J, Coxon B, Yergev A, Schneerson R 2003. A newly discovered cholesteryl galactoside from Borrelia burgdorferi. Proc Natl Acad Sci USA 100(13): 7913–7918.CrossRefGoogle Scholar
  10. Benvenga S, Guarneri F, Vaccaio M, Santarpia L, Trimarchi F 2004. Homologies between proteins of Borrelia burgdorferi and thyroid autoantigens. Thyroid 14(11): 964–976.PubMedCrossRefGoogle Scholar
  11. Boggs JM, Moscarello MA 1978. Structural organization of the human myelin membrane. Biochim Biophys Acta 515: 1–21.PubMedGoogle Scholar
  12. Brorson O, Brorson SH, Henriksen TH, Skogen PR, Schoven R 2001. Association between multiple sclerosis and cystic structures in cerebrospinal fluid. Infection 29(6): 315–319.PubMedCrossRefGoogle Scholar
  13. Brown JS 1996. Geographic correlation of multiple sclerosis with tick-borne diseases. Mult Scler 1: 257–261.PubMedGoogle Scholar
  14. Chmielewska-Badora J, Cisak E, Dutkiewicz J 2002. Lyme borreliosis and multiple sclerosis: Any connection? A seroepidemic study. Ann Agric Environ Med 7(2): 141–153.Google Scholar
  15. Contini C, Cultrera R, Saraceni S, Castellazzi M, Granieri E, et al. 2004. Cerebrospinal fluid molecular demonstration of Chlamydia pneumoniae DNA is associated to clinical and brain magnetic resonance imaging activity in a subset of patients with relapse-remitting multiple sclerosis. Mult Scler 10(4): 360–369.PubMedCrossRefGoogle Scholar
  16. Cumings JN 1955. Lipid chemistry of the brain in demyelinating diseases. Brain 78: 554–563.PubMedCrossRefGoogle Scholar
  17. De Libero G, Donda A, Gober HJ 2002. A new aspect in glycolipid biology: Glycosphingolipids as antigens recognized by T lymphocytes. Neurochem Res 27: 675–685.PubMedCrossRefGoogle Scholar
  18. De Libero G, Mori L 2003. Self glycosphingolipids: New antigens recognized by autoreactive T lymphocytes. News Physiol Sci 18: 71–76.PubMedGoogle Scholar
  19. De Libero G, Moran AP, Gober HJ 2005. Bacterial infections promote T cell recognition of self-glycolipids. Immunity 22(6): 763–772.PubMedCrossRefGoogle Scholar
  20. de Rosbo NK, Ben-Nun A 1998. T-cell responses to myelin antigens in multiple sclerosis; relevance of the predominant autoimmune reactivity to myelin oligodendrocyte glycoprotein. J Autoimmun 11: 287–299.PubMedCrossRefGoogle Scholar
  21. Dev KK, Mullershausen F, Mattes H, Kuhn RR, BilbeG, et al. 2008. Brain sphingosine-1-phosphate receptors: Implication for FTY720 in the treatment of multiple sclerosis. Pharmacol Therap 117: 77–93.CrossRefGoogle Scholar
  22. Dhib-Jalbut S 2007. Pathogenesis of myelin/oligodendrocyte damage in multiple sclerosis. Neurology 68(S3): S13–21.PubMedCrossRefGoogle Scholar
  23. Dong-Si T, Weber J, Liu YB, Buhmann C, BauerH, et al. 2004. Increased prevalence of and gene transcription by Chlamydia pneumoniae in cerebrospinal fluid of patients with relapsing–remitting multiple sclerosis. J Neurol 251(5): 542–547.PubMedCrossRefGoogle Scholar
  24. Egg R, Reindl M, Deisenhammer F, Linington C, Berger T 2001. Anti-MOG and anti-MBP antibody subclasses in multiple sclerosis. Mult Scler 7(5): 285–289.PubMedGoogle Scholar
  25. Endo T, Scott DD, Stewart SS, Kundu SK, Marcus DM 1984. Antibodies to glycosphingolipids in patients with multiple sclerosis and SLE. J Immunol 132: 1793–1797.PubMedGoogle Scholar
  26. Franklin GM, Nelson L 2003. Environmental risk factors in multiple sclerosis: Causes, triggers, and patient autonomy. Neurology 61(8): 1032–1034.PubMedGoogle Scholar
  27. Fredman P 1998. The role of antiglycolipid antibodies in neurological disorders. Ann NY Acad Sci 845: 341–352.PubMedCrossRefGoogle Scholar
  28. Fritzsche M 2005. Chronic Lyme borreliosis at the root of multiple sclerosis – is a cure with antibiotics attainable? Med. Hypotheses 64(3): 438–448.CrossRefGoogle Scholar
  29. Fry JM, Weissbarth S, Lehrer GM, Bornstein MB 1974. Cerebroside antibody inhibits sulfatide synthesis and myelination and demyelinates in cord tissue cultures. Science 183(124): 540–542.PubMedCrossRefGoogle Scholar
  30. Gerstl B, Kahnke MJ, Smith JK, Tavaststjerna MG, Hayman RB 1961. Brain lipids in multiple sclerosis and other diseases. Brain 84: 310–319.PubMedCrossRefGoogle Scholar
  31. Giovannoni G, Morris PR, Keir G 2000. Circulating antiganglioside antibodies are not associated with the development of progressive disease or cerebral atrophy in patients with multiple sclerosis. Ann Neurol 47: 684–685.PubMedCrossRefGoogle Scholar
  32. Godfrey DI, Hammond KJ, Poulton LD, Smyth MJ, Baxter AG 2000. NKT cells: Facts, functions and fallacies. Immunol Today 21: 573–583.PubMedCrossRefGoogle Scholar
  33. Goetzl EJ, Rosen H 2004. Regulation of immunity by lysosphingolipids and their G protein-coupled receptors. J Clin Invest 114: 1531–1537.PubMedGoogle Scholar
  34. Gross DM, Forsthuber T, Tary-Lehmann M, Etling C, ItoK, et al. 1998. Identification of LFA-1 as a candidate autoantigen in treatment resistant Lyme arthritis. Science 281(5377): 703–706.PubMedCrossRefGoogle Scholar
  35. Hammond KJ, Godfrey DI 2002. NKT cells: Potential targets for autoimmune disease therapy?. Tissue Antigens 59: 353–363.PubMedCrossRefGoogle Scholar
  36. Kanter JL, Narayana S, Ho PP, Catz I, WarrenKG, et al. 2006. Lipid microarrays identify key mediators of autoimmune brain inflammation. Nat Med 12(1): 138–143.PubMedCrossRefGoogle Scholar
  37. Kasai N, Pachner AR, Yu RK 1986. Anti-glycolipid antibodies and their immune complexes in multiple sclerosis. J Neurol Sci 75(1): 33–42.PubMedCrossRefGoogle Scholar
  38. Kinjo Y, Tupin E, Wu D, Fujio M, Garcia-Navarro R, et al. 2006. Natural killer T cells recognize diacylglycerol antigens from pathogenic bacteria. Nat Immunol. 7(9): 978–985.PubMedCrossRefGoogle Scholar
  39. Kinjo Y, Wu D, Kim G, Xing GW, PolesMA, et al. 2005. Recognition of bacterial glycosphingolipids by natural killer T cells. Nature 434(7032): 520–525.PubMedCrossRefGoogle Scholar
  40. Kronenberg M, Kinjo Y 2005. Infection, autoimmunity, and glycolipids: T cells detect microbes through self-recognition. Immunity 22(6): 657–659.PubMedCrossRefGoogle Scholar
  41. Kurtzke JF 2006. Multiple sclerosis in time and space – geographic clues to cause. J Neurovirol 6(S2): S134–140.Google Scholar
  42. Ilvas AA, Chen ZW, Cook SD 2003. Antibodies to sulfatide in cerebrospinal fluid of patients with multiple sclerosis. J Neuroimmunol 139: 76–80.CrossRefGoogle Scholar
  43. Ishii I, Fukushima N, Ye X and Chun J 2004. Lysophospholipid receptors: Signaling and biology. Annu Rev Biochem 73: 321–354.PubMedCrossRefGoogle Scholar
  44. Joyce S 2001. CD1d and natural T cells: How their properties jump-start the immune system. Cell Mol Life Sci 58: 442–469.PubMedCrossRefGoogle Scholar
  45. Lalive PH, Menge T, Delarasse C, Della Gaspera B, Pham-DinhD, et al. 2006. Antibodies to native myelin oligodendrocyte glycoprotein are serologic markers of early inflammation in multiple sclerosis. Proc Natl Acad Sci USA 103: 2280–2285.PubMedCrossRefGoogle Scholar
  46. Laloux V, Beaudoin L, Jeske D, Carnaud C, Lehuen A 2001. NK T cell-induced protection against diabetes in Vα14-Jα281 transgenic nonobese diabetic mice is associated with a Th2 shift circumscribed regionally to the islets and functionally to islet autoantigen. J Immunol 166: 3749–3756.PubMedGoogle Scholar
  47. Lana-Peixoto MA 1994. Multiple sclerosis and positive Lyme serology. Arq Neuropsiquiatr 52(4): 566–571.PubMedGoogle Scholar
  48. Libbey JE, McCoy LL, Fujinami RS 2007. Molecular mimicry in multiple sclerosis. Int Rev Neurobiol 79: 127–147.PubMedCrossRefGoogle Scholar
  49. Linsen L, Somers V, Stinissen P 2005. Immunoregulation of autoimmunity by natural killer T cells. Hum Immunol 66(12): 1193–1202.PubMedCrossRefGoogle Scholar
  50. Maida E 1983. Immunological reactions against Mycoplasma pneumoniae in multiple sclerosis: Preliminary findings. J Neurol 229(2): 103–111.PubMedCrossRefGoogle Scholar
  51. Mandala S, Hajdu R, Bergstrom J, Quackenbush E, XieJ, et al. 2002. Alteration of lymphocyte trafficking by sphingosine-1-phosphate receptor agonists. Science 296: 346–349.PubMedCrossRefGoogle Scholar
  52. Mattner J, Debord KL, Ismail N, Goff RD, Cantu C 3rd, et al. 2005. Exogenous and endogenous glycolipid antigens activate NKT cells during microbial infections. Nature 434(7032): 525–529.PubMedCrossRefGoogle Scholar
  53. Menon KK, Piddlesden SJ, Bernard CC 1997. Demyelinating antibodies to myelin oligodendrocyte glycoprotein and galactocerebroside induce degradation of myelin basic protein in isolated human myelin. J Neurochem 69(1): 214–222.PubMedCrossRefGoogle Scholar
  54. Merril AH 2002. De novo sphingolipid biosynthesis: A necessary but dangerous pathway. J Biol Chem 277: 25843–25846.CrossRefGoogle Scholar
  55. Miron VE, Jung CG, Kim HJ, Kennedy TE, SolivenB, et al. 2008. FTY720 modulates human oligodendrocyte progenitor process extension and survival. Ann Neurol 63: 61–71.PubMedCrossRefGoogle Scholar
  56. Morell P, and Norton WT 1980. Myelin. Sci Am 242: 88–90.PubMedCrossRefGoogle Scholar
  57. Moses H, Sriram S 2001. An infectious basis for multiple sclerosis: Perspectives on the role of Chlamydia pneumoniae and other agents. Bio Drugs 15(3): 199–206.Google Scholar
  58. Pfeiffer SE, Warrington AE, Bansal R 1993. The oligodendrocyte and its many cellular processes. Trends Cell Biol 3(6): 191–197.PubMedCrossRefGoogle Scholar
  59. Porubsky S, Speak AO, Luckow B, Cerundolo V, PlattFM, et al. 2007. Normal development and function of invariant natural killer T cells in mice with isoglobotrihexosylceramide (igb3) deficiency. Proc Natl Acad Sci USA 104: 5977–5982.PubMedCrossRefGoogle Scholar
  60. Raine CS, Johnson AB, Marcus DM, Suzuki A, Bornstein MB 1981. Demyelination in vitro: Absorption studies demonstrate that galactocerebroside is a major target. J Neurol Sci 52(1): 117–131.PubMedCrossRefGoogle Scholar
  61. Reindl M, Linington C, Brehm U 1999. Antibodies against the myelin oligodendrocyte glycoprotein and the myelin basic protein in multiple sclerosis and other neurological diseases: A comparative study. Brain 122: 2047–2056.PubMedCrossRefGoogle Scholar
  62. Sadatipour BT, Greer JM, Pender MP 2000. Increased circulating antiganglioside antibodies in primary and secondary progressive multiple sclerosis. Ann Neurol 47(5): 684–685.Google Scholar
  63. Sanchez T, Hla T 2004. Structural and functional characteristics of S1P receptors. J Cell Biochem 92: 913–922.PubMedCrossRefGoogle Scholar
  64. Sawicka E, Dubois G, Jarai G, Edwards M, ThomasM, et al. 2005. The sphingosine 1-phosphate receptor agonist FTY720 differentially affects the sequestration of CD4_/CD25_ T-regulatory cells and enhances their functional activity. J Immunol 175: 7973–7980.PubMedGoogle Scholar
  65. Schwid SR, Goodman AD, Mattson DH 1997. Autoimmune hyperthyroidism in patients with multiple sclerosis treated with interferon beta-1b. Arch Neurol 54(9): 1169–1190.PubMedGoogle Scholar
  66. Shamshiev A, Donda A, Carena I, Mori L, KapposL, et al. 1999. Self glycolipids as T-cell autoantigens. Eur J Immunol 29(5): 1667–1675.PubMedCrossRefGoogle Scholar
  67. Shamshiev A, Donda A, Prigozy TI, Mori L, ChigornoV, et al. 2000. The alphabeta T cell response to self-glycolipids shows a novel mechanism of CD1b loading and a requirement for complex oligosaccharides. Immunity 13: 255–264.PubMedCrossRefGoogle Scholar
  68. Shi FD, Flodstrom M, Balasa B, Kim SH, Van Gunst K, et al. 2001. Germ line deletion of the CD1 locus exacerbates diabetes in the NOD mouse. Proc Natl Acad Sci USA 98: 6777–6782.PubMedCrossRefGoogle Scholar
  69. Speak AO, Salio M, Neville DC, Fontaine J, Priestman DA, et al. 2007. Implications for invariant natural killer T cell ligands due to the restricted presence of isoglobotrihexosylceramide in mammals. Proc Natl Acad Sci USA 104(14): 5971–5976.PubMedCrossRefGoogle Scholar
  70. Sriram V, Du W, Gervay-Hague J, Brutkiewicz RR 2005. Cell wall glycosphingolipids of Sphingomonas paucimobilis are CD1dspecific ligands for NKT cells. Eur J Immunol. 35(6): 1692–1701.PubMedCrossRefGoogle Scholar
  71. Steere AC, Gross D, Meyer AL, Huber BT 2001. Autoimmune mechanisms in antibiotic treatment-resistant Lyme arthritis. J Autoimmun 16(3): 263–268.PubMedCrossRefGoogle Scholar
  72. Stevens A, Weller M, Wietholter H 1992. CSF and serum ganglioside antibody patterns in MS. Acta Neurol Scand 86: 485–489.PubMedCrossRefGoogle Scholar
  73. Stinissen P, Raus J, Zhang J 1997. Autoimmune pathogenesis of multiple sclerosis: Role of autoreactive T lymphocytes and new immunotherapeutic strategies. Crit Rev Immunol 17(1): 33–75.PubMedGoogle Scholar
  74. Tupin E, Kinjo Y, Kronenberg M 2007. The unique role of natural killer T cells in the response to microorganisms. Nat Rev Microbiol 5(6): 405–417.PubMedCrossRefGoogle Scholar
  75. Uhlig H, Dernick R 1989. Monoclonal autoantibodies derived from multiple sclerosis patients and control persons and their reactivities with antigens of the central nervous system. Autoimmunity 5: 87–99.PubMedCrossRefGoogle Scholar
  76. Wang B, Geng YB, Wang CR 2001. CD1-restricted NK T cells protect nonobese diabetic mice from developing diabetes. J Exp Med 194: 313–320.PubMedCrossRefGoogle Scholar
  77. Williams KC, Ulvestad E, Hickey WF 1994. Immunology of multiple sclerosis. Clin Neurosci 2: 229–245.PubMedGoogle Scholar
  78. Wolfson C, Talbot P 2002. Bacterial infection as a cause of multiple sclerosis. Lancet 360: 352–3.PubMedCrossRefGoogle Scholar
  79. Wu D, Zajonc DM, Fujio M, Sullivan BA, KinjoY, et al. 2006. Design of natural killer T cell activators: structure and function of a microbial glycosphingolipid bound to mouse CD1d. Proc Natl Acad Sci USA 103(11): 3972–3977.PubMedCrossRefGoogle Scholar
  80. Zajonc DM, Maricic I, Wu D, Halder R, Roy K, et al. 2005. Structural basis for CD1d presentation of a sulfatide derived from myelin and its implications for autoimmunity. J Exp Med 202: 1517–1526.PubMedCrossRefGoogle Scholar
  81. Zhou D, Mattner J, Cantu C 3rd, Schrantz N, YinN, et al. 2004. Lysosomal glycosphingolipid recognition by NKT cells. Science 306(5702): 1786–1789.PubMedCrossRefGoogle Scholar
  82. Yamazaki M, Thorne L, Mikolajczak M, Armentrout RW, Pollock TJ 1996. Linkage of genes essential for synthesis of a polysaccharide capsule in Sphingomonas strain S88. J Bacteriol 178(9): 2676–2687.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • L. Rinaldi
  • F. Grassivaro
  • P. Gallo

There are no affiliations available

Personalised recommendations