MHC and Non-MHC Genetics of Experimental Autoimmune Encephalomyelitis

  • T. Olsson
  • I. Dahlman
  • E. Wallström
Part of the Topics in Neuroscience book series (TOPNEURO)


Our present understanding of the ethiopathogenesis of multiple sclerosis (MS) and its experimental models, e.g. various forms of experimental autoimmune encephalomyelitis (EAE), includes three cornerstones: (1) autoimmunity to components of the central nervous system (CNS), (2) genetic predisposition, and (3) environmental influences.


Multiple Sclerosis Experimental Autoimmune Encephalomyelitis Experimental Allergic Encephalomyelitis Myelin Oligodendrocyte Glycoprotein Congenic Strain 
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.


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  1. 1.
    Ebers GC, Bulman D, Sadovnick A et al. (1986) A population-based twin study in multiple sclerosis. N Eng J Med 315: 1638–1642CrossRefGoogle Scholar
  2. 2.
    Ebers GC, Sadovnick AD, Risch NJ and the Canadian Collaborative Study Group (1995) A genetic basis for familial aggregation in multiple sclerosis. Nature 377:150–151PubMedCrossRefGoogle Scholar
  3. 3.
    Sadovnick AD, Ebers GC, Dyment DA, Risch NJ and the Canadian Collaborative Study Group (1996) Evidence for genetic basis of multiple sclerosis. The Lancet 347: 1728–1730CrossRefGoogle Scholar
  4. 4.
    Risch N (1990) Linkage strategies for genetically complex traits. I. Multilocus models. Am J Hum Gen 46: 222–228Google Scholar
  5. 5.
    Olerup O, Hillert J (1991) HLA class II associated genetic susceptibility in multiple sclerosis: A critical evaluation. Tissue Antigens 38:1–15PubMedCrossRefGoogle Scholar
  6. 6.
    Ebers GC, Kukay K, Bulman DE et al. (1996) A full genome search in multiple sclerosis. Nat Genet 13: 472–476PubMedCrossRefGoogle Scholar
  7. 7.
    Sawcer S, Jones HB, Feakes R et al. (1996) A genome screen in multiple sclerosis reveals susceptibility loci on chromosome 6p21 and 17q22. Nat Genet 13: 464–468PubMedCrossRefGoogle Scholar
  8. 8.
    The Multiple Sclerosis Genetics Group (1996) A complete genomic screen for multiple sclerosis underscores a role for the major histocompatibility complex. Nat Genet 13: 469–471CrossRefGoogle Scholar
  9. 9.
    Ebers GC, Sadovnick AD (1994) The role of genetic factors in multiple sclerosis susceptibility. J Neuroimmunol 54: 1–17PubMedCrossRefGoogle Scholar
  10. 10.
    Haines JL, Terwedow HA, Burgess K et al. (1998) Linkage of the MHC to familial multiple sclerosis suggests genetic heterogeneity. Human Mole Genet 7:1229–1234CrossRefGoogle Scholar
  11. 11.
    Hillert J (1996) Genetics of multiple sclerosis. In: Cook S (ed) Handbook of multiple sclerosis. Marcel Dekker, New York, pp 19–51Google Scholar
  12. 12.
    Marrosu MG, Murru MR, Costa G et al. (1998) DRB1-DQA1-DQB1 loci and multiple sclerosis predisposition in the Sardinian population. Hum Mole Genet 7: 1235–1237CrossRefGoogle Scholar
  13. 13.
    Hillert J, Olerup O (1993) Multiple sclerosis is associated with genes within or close to the HLA-DR-DQ subregion on a normal DR15, DQ6DW 2 haplotype. Neurology 43: 163 (abstract)PubMedCrossRefGoogle Scholar
  14. 14.
    Wallström E, Khademi M, Andersson M et al. (1998) Increased reactivity to myelin oligodendrocyte glycoprotein peptides and epitope mapping in DR2(15)+ multiple sclerosis. Eur J Immunol 28: 3329–3335PubMedCrossRefGoogle Scholar
  15. 15.
    Fogdell-Hahn A, Ligers A, Grönning M et al. (1998) Multiple sclerosis: a modifying influence of HLA class I genes in an HLA class II associated disease. Eur J Immunogenet 25(Suppl 1): 62Google Scholar
  16. 16.
    Kuokkanen S, Gschend M, Rioux JD et al. (1997) Genomewide scan of multiple sclerosis in Finnish multiplex families. Am J Hum Genet 61:1379–1387PubMedCrossRefGoogle Scholar
  17. 17.
    Chataway J, Feakes R, Corraddu F et al. (1998) The genetics of multiple sclerosis: principles, background and updated results of the United Kingdom systematic genome screen. Brain 121:1869–1887PubMedCrossRefGoogle Scholar
  18. 18.
    Janson C, Olsson T, Höjeberg B, Holmdahl R (1991) Chronic experimental allergic encephalomyelitis induced by the 89–110 myelin basic protein peptide in mice with I-Ar. Eur J Immunol 21:693–699CrossRefGoogle Scholar
  19. 19.
    Brown A, McFarlin DE, Raine CS (1982) Chronologic neuropathology of relapsing experimental allergic encephalomyelitis in the mouse. Lab Invest 46: 171–185PubMedGoogle Scholar
  20. 20.
    Baker D, O’Neill JK, Gschmeissner SE et al. (1990) Induction of chronic relapsing allergic encephalomyelitis in Biozzi mice. J Neuroimmunol 28: 261–270PubMedCrossRefGoogle Scholar
  21. 21.
    Lorentzen JC, Glaser A, Jacobsson L et al. (1998) Identification of rat susceptibility loci for adjuvant-oil induced arthritis. Proc Natl Acad Sci USA 95: 6383–6387PubMedCrossRefGoogle Scholar
  22. 22.
    Vingsbo C, Sahistrand P, Brun JG et al. (1996) Pristane-induced arthritis in rats: a new model for rheumatoid arhtritis with a chronic disease course influenced by both major histocompatibility complex and non-major histocompatibility complex genes. Am J Pathol 149: 1675–1683PubMedGoogle Scholar
  23. 23.
    Vingsbo-Lundberg C, Nordquist N, Olofsson P et al. (1998) Genetic control of arthritis onset, severity and chronicity in a model for rheumatoid arthritis in rats. Nat Genet 20: 401–404PubMedCrossRefGoogle Scholar
  24. 24.
    Lorentzen J, Issazadeh S, Storch M et al. (1995) Protracted, relapsing and demyelinating experimental autoimmune encephalomyelitis in DA rats, immunized wtih syngeneic spinal cord and incomplete Freund’s adjuvant. J Neuroimmunol 63:193–205PubMedCrossRefGoogle Scholar
  25. 25.
    Storch MK, Stefferl A, Brehm U et al. (1998) Autoimmunity to myelin oligodendrocyte glycoprotein mimics the spectrum of multiple sclerosis pathology. Brain Pathology 8: 681–694PubMedCrossRefGoogle Scholar
  26. 26.
    Weissert R, Wallström E, Storch M et al. (1998) MHC haplotype dependent regulation of clinical profile and lesional pathology of myelin oligodendrocyte glycoprotein induced experimental autoimmune encephalomyelitis. J Clin Invest 102:1265–1273PubMedCrossRefGoogle Scholar
  27. 27.
    Berger T, Weerth S, Kojima K et al. (1997) Experimental autoimmune encephalomyelitis: the antigen specificity of T lymphocytes determines the topography of lesions in the central and peripheral nervous system. Lab Invest 76: 355–364PubMedGoogle Scholar
  28. 28.
    Adelmann M, Wood J, Benzel I et al. (1995) The N-terminal domain of the myelin oligodendrocyte glycoprotein (MOG) induces acute demyelinating experimental autoimmune encephalomyelitis in the Lewis rat. J Neuroimmunol 63:17–27PubMedCrossRefGoogle Scholar
  29. 29.
    Hedrich HJ (ed) (1990) Genetic monitoring of inbred strains of rats. Gustav Fischer, Stuttgart New YorkGoogle Scholar
  30. 30.
    Frankel WN (1995) Taking stock of complex trait genetics in mice. Trends Genet 11:471–477PubMedCrossRefGoogle Scholar
  31. 31.
    Mapmaker reference:
  32. 32.
    Lander E, Kruglyak L (1995) Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nat Genet 11: 241–247PubMedCrossRefGoogle Scholar
  33. 33.
    Microsatellite maps:
  34. 34.
    Snell GD (1948) J Genet 49: 87–99PubMedCrossRefGoogle Scholar
  35. 35.
    Wakeland E, Morel L, Achey K et al. (1997) Speed congenics: a classic technique in the fast lane (relatively speaking). Immunol Today 18: 472–477PubMedCrossRefGoogle Scholar
  36. 36.
    Markel P, Shu P, Ebeling C et al. (1997) Theoretical and empirical issues for marker-assisted breeding of congenic mouse strains. Nat Genet 17: 280–284PubMedCrossRefGoogle Scholar
  37. 37.
    Comparative maps
  38. 38.
    Brunsberg U, Gustafsson K, Jansson L et al. (1994) Expression of a transgenic class II Ab gene confers susceptibility to collagen-induced arthritis. Eur J Immunol 24:1698–1702PubMedCrossRefGoogle Scholar
  39. 39.
    Williams RM, Moore MJ (1973) Linkage of susceptibility to experimental allergic encephalomyelitis to the major histocompatibility complex locus in the rat. J Exp Med 138: 775–783PubMedCrossRefGoogle Scholar
  40. 40.
    Fritz RB, Skeen MJ, Jen Chou CH et al. (1985) Major histocompatibility complex-linked control of the murine immune response to myelin basic protein. J Immunol 134: 2328–2332PubMedGoogle Scholar
  41. 41.
    Jansson L, Olsson T, Höjeberg B, Holmdahl R (1991) Chronic experimental allergic encephalomyelitis induced by the 89–101 myelin basic protein peptide in mice with I-Ar. Eur J Immunol 21: 693–699PubMedCrossRefGoogle Scholar
  42. 42.
    Lorentzen J, Andersson M, Issazadeh S et al. (1997) Genetic analysis of inflammation, cytokine mRNA expression and disease course of relapsing experimental autoimmune encephalomyelitis in DA rats. J Neuroimmunol 80: 31–37PubMedCrossRefGoogle Scholar
  43. 43.
    Mustafa M, Vingsbo C, Olsson T, Issazadeh S, Ljungdahl Å, Holmdahl R (1994) Alleles of both MHC class I and II regions have protective roles in MBP 63–88 induced EAE in rats. J Immunol 153: 3337–3344.PubMedGoogle Scholar
  44. 44.
    Issazadeh S, Kjellen P, Olsson T et al. (1997) Major histocompatibility complex-controlled protective influences on experimental autoimmune encephalomyelitis are peptide specific. Eur J Immunol 27:1584–1587PubMedCrossRefGoogle Scholar
  45. 45.
    de Graaf KL, Weissert R, Kjellen P et al. (1999) Allelic variations in rat MHC class II binding of myelin basic protein peptides correlate with encephalitogenicity. (Manuscript submitted)Google Scholar
  46. 46.
    Pfeiffer C, Stein J, Southwood S et al. (1995) Altered peptide ligands can control CD4 T lymphocyte differentiation in vivo. J Exp Med 181:1569–1574PubMedCrossRefGoogle Scholar
  47. 47.
    Murray JS (1998) How the MHC selects Thl/Th2 immunity. Immunol Today 19:157–163PubMedCrossRefGoogle Scholar
  48. 48.
    Sundvall M, Jirholt J, Yang HT et al. (1995) Identification of murine loci associate with susceptibility to chronic experimental autoimmune encephalomyelitis. Nat Genet 10: 313–317PubMedCrossRefGoogle Scholar
  49. 49.
    Encinas JA, Lees MB, Sobel RA et al. (1996) Genetic analysis of susceptibility to experimental autoimmune encephalomyelitis in a cross between SJL/J and BIO S mice. J Immunol 157: 2186–2192PubMedGoogle Scholar
  50. 50.
    Baker D, Rosenwasser OA, O’Neill JK, Turk JL (1995) Genetic analysis of experimental allergic encephalomyelitis in mice. J Immunol 155: 4046–4051PubMedGoogle Scholar
  51. 51.
    Butterfield RJ, Sudweeks JD, Blankenhorn EP et al. (1998) New genetic loci that control susceptibility and symptoms of experimental allergic encephalomyelitis in inbred mice. J Immunol 161:1860–1867PubMedGoogle Scholar
  52. 52.
    Kjellen P, Issazadeh S, Olsson T, Holmdahl R (1998) Genetic influence on disease course and cytokine response in relapsing experimental allergic encephalomyelitis. International Immunol 10: 333–340CrossRefGoogle Scholar
  53. 53.
    Dahlman I, Jacobsson L, Glaser A et al. (1999) A genome-wide linkage analysis of chronic relapsing experimental autoimmune encephalomyelitis in the rat identifies a major susceptibility locus on chromosome 9. J Immunol (in press)Google Scholar
  54. 54.
    Dahlman I, Lorentzen JC, de Graaf KL et al. (1998) Quantitative trait loci disposing for both experimental arthitis and encephalomyelitis in the DA rat; impact on severity of myelin oligodendrocyte glycoprotein-induced EAE and antibody isotype pattern. Eur J Immunol 28: 2188–2196PubMedCrossRefGoogle Scholar
  55. 55.
    Becker KG, Simon RM, Bailey-Wilson JE et al. (1998) Clustering of non-major histocompatibility complex susceptibility candidate loci in human autoimmune diseases. Proc Natl Acad Sci USA 95: 9979–9984PubMedCrossRefGoogle Scholar
  56. 56.
    Kuokkanen S, Sundvall M, Terwilliger JD et al. (1996) A putative vulnerability locus to multiple sclerosis maps to 5 p14-p12 in a region syntenic to the murine locus Eae2. Nat Genet 13: 477–480PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia 1999

Authors and Affiliations

  • T. Olsson
    • 1
  • I. Dahlman
    • 1
  • E. Wallström
    • 1
  1. 1.Neuroimmunology Unit, Centre for Molecular Medicine, Department of MedicineKarolinska InstitutetStockholmSweden

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