Idiopathic Inflammatory Myopathies: Immunological Aspects

  • R. Mantegazza
  • P. Bernasconi
  • F. Cornelio
Part of the Topics in Neuroscience book series (TOPNEURO)


Muscle inflammation is generally termed “myositis” whether the aetiology is known (viral, bacterial or parasitic) or unknown (idiopathic). The inflammatory myopathies are a heterogeneous group of subacute/chronic muscle disorders sharing a common characteristic muscle degeneration mediated by inflammatory mechanisms [1]. This review will be concerned with the main pathogenetic features of the three major inflammatory myopathies: dermatomyositis (DM), polymyositis (PM) and inclusion body myositis (IBM). The latter includes sporadic (s-IBM) and hereditary inclusion body myopathy (h-IBM), which is an a hereditary progressive muscle disease with muscle pathology similar to the s-IBM,but lacking lymphocytic inflammation [2].


Major Histocompatibility Complex Class Muscle Biopsy Inclusion Body Myositis Inflammatory Myopathy Idiopathic Inflammatory Myopathy 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Dalakas MC (1998) Molecular immunology and genetics of inflammatory muscle diseases. Arch Neurol 55:1509–1512PubMedCrossRefGoogle Scholar
  2. 2.
    Askanas V, Serratrice G, Engel WK (eds) (1998) Inclusion-body myositis and myopathies. Cambridge University Press, CambridgeGoogle Scholar
  3. 3.
    Engel AG, Hohlfeld R, Banker BQ (1994) Inflammatory myopathies. The polymyositis and dermatomyositis syndromes. In: Engel AG, Franzini-Armstrong C (eds) Myology. McGraw-Hill, New York, pp 1335–1383Google Scholar
  4. 4.
    Ioannou Y, Sultan S, Isenberg D (1999) Myositis overlap syndromes. Curr Opin Rheumatol 11:468–474PubMedCrossRefGoogle Scholar
  5. 5.
    Miller FW (1993) Myositis-specific autoantibodies. Touchstones for understanding the inflammatory myopathies. JAMA 270:1846–1849.PubMedCrossRefGoogle Scholar
  6. 6.
    Mantegazza R, Baggi F, Bernasconi P (2001) Methods for examination of antibodies in skeletal muscle disease. In: Preedy VR, Peters TJ (eds) Skeletal muscle: pathology, diagnosis and management of disease. Greenwich Medical Media, London (in press)Google Scholar
  7. 7.
    Basta M, Dalakas MC (1994) High dose intravenous immunoglobulin exerts its beneficial effect in patients with dermatomyositis by blocking endomysial deposition of activated complement fragments. J Clin Invest 94:1729–1735PubMedCrossRefGoogle Scholar
  8. 8.
    Amemiya K, Granger RP, Dalakas MC (2000) Clonal restriction of T-cell receptor expression by infiltrating lymphocytes in inclusion body myositis persists over time: studies in repeated muscle biopsies. Brain 123:2030–2039PubMedCrossRefGoogle Scholar
  9. 9.
    Cherin P (1999) Treatment of inclusion body myositis. Curr Opin Rheumatol 11:456–461PubMedCrossRefGoogle Scholar
  10. 10.
    Engel AG, Arahata K (1984) Monoclonal antibody analysis of mononuclear cells in myopathies. II: phenotypes of autoinvasive cells in polymyositis and inclusion body myositis. Ann Neurol 16:209–215PubMedCrossRefGoogle Scholar
  11. 11.
    De Bleecker JL, Engel AG (1994) Expression of cell adhesion molecules in inflammatory myopathies and Duchenne dystrophy. J Neuropathol Exp Neurol 53:369–376PubMedCrossRefGoogle Scholar
  12. 12.
    De Bleecker JL, Engel AG (1995) Immunocytochemical study of CD45 T cell isoforms in inflammatory myopathies. Am J Pathol 146:1178–1187PubMedGoogle Scholar
  13. 13.
    Pruitt JN, Showalter CJ, Engel AG (1996) Sporadic inclusion body myositis: counts of different types of abnormal fibers. Ann Neurol 39:139–143PubMedCrossRefGoogle Scholar
  14. 14.
    Kissel JT, Mendell JR, Rammohan KW (1986) Microvascular deposition of complement membrane attack complex in dermatomyositis. N Engl J Med 314:331–334CrossRefGoogle Scholar
  15. 15.
    Emslie-Smith AM, Engel AG (1990) Microvascular changes in early and advanced dermatomyositis: a quantitative study. Ann Neurol 27:343–356PubMedCrossRefGoogle Scholar
  16. 16.
    Germain RN, Margulies DH (1993) The biochemistry and cell biology of antigen processing and presentation. Annu Rev Immunol 11:403–450PubMedCrossRefGoogle Scholar
  17. 17.
    Emslie-Smith AM, Arahata K, Engel AG (1989) Major histocompatibility complex class I antigen expression, immunolocalization of interferon subtypes, and T cell-mediated cytotoxicity in myopathies. Hum Pathol 20:224–231PubMedCrossRefGoogle Scholar
  18. 18.
    Nagaraju K, Raben N, Loeffler L et al (2000) Conditional up-regulation of MHC class I in skeletal muscle leads to self-sustaining autoimmune myositis and myositis-specific autoantibodies. Proc Natl Acad Sci USA 97:9209–9214PubMedCrossRefGoogle Scholar
  19. 19.
    Mantegazza R, Hughes SM, Mitchell D et al (1991) Modulation of MHC class II antigen expression in human myoblasts after treatment with IFN-γ. Neurology 41:1128–1132PubMedCrossRefGoogle Scholar
  20. 20.
    Holhfeld R, Engel AG (1990) Induction of HLA-DR expression on human myoblasts with interferon-gamma. Am J Pathol 136:503–508Google Scholar
  21. 21.
    Goebels N, Michaelis D, Wekerle H, Hohlfeld R (1992) Human myoblasts as antigen-presenting cells. J Immunol 149:661–667PubMedGoogle Scholar
  22. 22.
    Mantegazza R, Gebbia M, Mora M, Barresi R, Bernasconi P, Baggi F, Cornelio F (1996) Major histocompatibility complex class II molecule expression on muscle cells is regulated by differentiation: implications for the immunopathogenesis of muscle autoimmune diseases. J Neuroimmunol 68:53–60PubMedCrossRefGoogle Scholar
  23. 23.
    Beauchamp IR, Abraham DJ, Bou-Gharios G, Partridge TA, Olsen I (1992) Expression and function of heterotypic adhesion molecules during differentiation of human skeletal muscle in culture. Am J Pathol 140:387–401PubMedGoogle Scholar
  24. 24.
    Michaelis D, Goebels N, Hohlfeld R (1993) Constitutive and cytokine-induced expression of human leukocyte antigens and cell adhesion molecules by human myotubes. Am J Pathol 143:1142–1149PubMedGoogle Scholar
  25. 25.
    Hardiman O, Faustman D, Li X, Sklar RM, Brown RH (1993) Expression of major his-tocompatibility complex antigens in cultures of clonally derived human myoblasts. Neurology 43:604–608PubMedCrossRefGoogle Scholar
  26. 26.
    Reiser H, Stadecker M J (1996) Costimulatory B7 molecules in the pathogenesis of infectious and autoimmune diseases. N Engl J Med 335:1369–1377PubMedCrossRefGoogle Scholar
  27. 27.
    Hohlfeld R, Engel AG (1994) The immunobiology of muscle. Immunol Today 15:269–274PubMedCrossRefGoogle Scholar
  28. 28.
    Bernasconi P, Confalonieri P, Andreetta F, Baggi F, Cornelio F, Mantegazza R (1998) The expression of co-stimulatory and accessory molecules on cultured human muscle cells is not dependent on stimulus by pro-inflammatory cytokines: relevance for the pathogenesis of inflammatory myopathy. J Neuroimmunol 85:52–58PubMedCrossRefGoogle Scholar
  29. 29.
    Freeman GJ, Cardoso AA, Boussiotis VA et al (1998) The BBl monoclonal antibody recognizes both cell surface CD74 (MHC class Il-associated invariant chain) as well as B7-1 (CD80), resolving the question regarding a third CD28/CTLA-4 counterreceptor. J Immunol 161:2708–2715PubMedGoogle Scholar
  30. 30.
    Beherens L, Kerschensteiner M, Misgeld T, Goebels N, Wekerle H, Hohlfeld R (1998) Human muscle cells express a functional costimulatory molecule distinct from B7.1 (CD80) and B7.2 (CD86) in vitro and in inflammatory lesions. J Immunol 161:5943–5951Google Scholar
  31. 31.
    Murata K, Dalakas MC (1999) Expression of the costimulatory molecule BB-1, the ligands CTLA-4 and CD28, and their mRNA in inflammatory myopathies. Am J Pathol 155:453–460PubMedCrossRefGoogle Scholar
  32. 32.
    Blau HM, Springer ML (1995) Muscle-mediated gene therapy. N Engl J Med 333:1554–1556PubMedCrossRefGoogle Scholar
  33. 33.
    Beherens L, Kerschensteiner M, Misgeld T, Goebels N, Wekerle H, Hohlfeld R (1998) Human muscle cells express a functional costimulatory molecule distinct from B7.1 (CD80) and B7.2 (CD86) in vitro and in inflammatory lesions. J Immunol 2000 164:5330 correction of ref 30Google Scholar
  34. 34.
    Garcia KG, Teyton L, Wilson IA (1999) Structural basis of T cell recognition. Ann Rev Immunol 17:369–397CrossRefGoogle Scholar
  35. 35.
    Davis MM, Boniface JJ, Reich Z et al (1998) Ligand recognition by αβ T cell receptors. Ann Rev Immunol 16:523–544CrossRefGoogle Scholar
  36. 36.
    Mantegazza R, Andreetta F, Bernasconi P et al (1993) Analysis of T cell receptor repertoire of muscle-infiltrating T lymphocytes in polymyositis. J Clin Invest 91:2880–2886PubMedCrossRefGoogle Scholar
  37. 37.
    Bender A, Ernst N, Iglesias A, Dornmair K, Wekerle H, Hohlfeld R (1995) T cell receptor repertoire in polymyositis: clonal expansion of autoaggressive CD8+ T cells. J Exp Med 181:1863–1868PubMedCrossRefGoogle Scholar
  38. 38.
    O’Hanlon TP, Dalakas MC, Plötz PH, Miller FW (1994) Predominant TCR-αβ variable and joining gene expression by muscle-infiltrating lymphocytes in the idiopathic inflammatory myopathies. J Immunol 152: 2569–2576PubMedGoogle Scholar
  39. 39.
    Pluschke G, Ruegg D, Hohlfeld R, Engel AG (1992) Autoaggressive myocytotoxic T lymphocytes expressing an unusual γ/δ T cell receptor. J Exp Med 176:1785–1789PubMedCrossRefGoogle Scholar
  40. 40.
    O’Hanlon TP, Messersmith WA, Dalakas MC, Plötz PH, Miller FW (1995) Gamma delta T cell receptor gene expression by muscle-infiltrating lymphocytes in the idiopathic inflammatory myopathies. Clin Exp Immunol 100:519–528PubMedCrossRefGoogle Scholar
  41. 41.
    Mantegazza R, Bernasconi P, Torchiana E et al (1994) Molecular analysis of T cell receptor repertoire of T cell infiltrates in sporadic and familial inclusion body myositis. Muscle Nerve 17 (Suppl 1):117Google Scholar
  42. 42.
    Lindberg C, Oldfors A, Tarkowski A (1994) Restricted use of T cell receptor V genes in endomysial infiltrates of patients with inflammatory myopathies. Eur J Immunol 24:2659–2663PubMedCrossRefGoogle Scholar
  43. 43.
    O’Hanlon TP, Dalakas MC, Plötz PH, Miller FW (1994) The αβ T-cell receptor repertoire in inclusion body myositis: diverse patterns of gene expression by muscle-infiltrating lymphocytes. J Autoimmunity 7:321–333CrossRefGoogle Scholar
  44. 44.
    Fyhr IM, Moslemi AR, Mosavi AA, Lindberg C, Tarkowski A, Oldfors A (1997) Oligoclonal expansion of muscle infiltrating T cells in inclusion body myositis. J Neuroimmunol 79:185–189PubMedCrossRefGoogle Scholar
  45. 45.
    Fyhr IM, Moslemi AR, Lindberg C, Oldfors A (1998) T cell receptor β-chain repertoire in inclusion body myositis. J Neuroimmunol 91:129–134PubMedCrossRefGoogle Scholar
  46. 46.
    Bender A, Behrens L, Engel AG, Hohlfeld R (1998) T-cell heterogeneity in muscle lesions of inclusion body myositis. J Neuroimmunol 84:86–91PubMedCrossRefGoogle Scholar
  47. 47.
    Janeway CA, Bottomly K (1994) Signals and signs for lymphocyte responses. Cell 76:275–285PubMedCrossRefGoogle Scholar
  48. 48.
    Andreetta F, Bernasconi P, Torchiana E, Baggi F, Cornelio F, Mantegazza R (1995) T-cell infihration in polymyositis is characterized by coexpression of cytotoxic and T-cellactivating cytokine transcripts. Ann N Y Acad Sci 756:418–420PubMedCrossRefGoogle Scholar
  49. 49.
    Lundberg I, Brengman JM, Engel AG (1995) Analysis of cytokine expression in muscle in inflammatory myopathies, Duchenne dystrophy, and non-weak controls. J Neuroimmunol 63:9–16PubMedCrossRefGoogle Scholar
  50. 50.
    Lundberg I, Ulfgren AK, Nyberg P, Andersson U, Klareskog L (1997) Cytokine production in muscle tissue of patients with idiopathic inflammatory myopathies. Arthritis Rheum 40:865–874PubMedCrossRefGoogle Scholar
  51. 51.
    Tews DS, Goebel HH (1996) Cytokine expression profile in idiopathic inflammatory myopathies. J Neuropathol Exp Neurol 55:342–347PubMedCrossRefGoogle Scholar
  52. 52.
    Authier FJ, Mhiri C, Chazaud B, Christov P, Barlovatz-Meimon G, Gherardi RK (1997) Interleukin-1 expression in inflammatory myopathies: evidence of marked immunoreactivity in sarcoid granulomas and muscle fibres showing ischaemic and regenerative changes. Neuropathol Appl Neurobiol 23:132–140PubMedCrossRefGoogle Scholar
  53. 53.
    De Bleecker JL, Meire VI, Declercq W, Van Aken EH (1999) Immunolocalization of tumor necrosis factor-alpha and its receptors in inflammatory myopathies. Neuromusc Disord 9:239–246PubMedCrossRefGoogle Scholar
  54. 54.
    Tateyama M, Nagano I, Yoshioka M, Chida K, Nakamura S, Itoyama Y (1997) Expression of tumor necrosis factor-alpha in muscles in polymyositis. J Neurol Sci 146:45–51PubMedCrossRefGoogle Scholar
  55. 55.
    Confalonieri P, Bernasconi P, Cornelio F, Mantegazza R (1997) Transforming growth factor-betal in polymyositis and dermatomyositis correlates with fibrosis but not with mononuclear cell infiltrate. J Neuropathol Exp Neurol 56:479–484PubMedCrossRefGoogle Scholar
  56. 56.
    Wahl SM (1994) Transforming growth factor β: the good, the bad and the ugly. J Exp Med 180:1587–1590PubMedCrossRefGoogle Scholar
  57. 57.
    Gamble JR, Khew-Goodall Y, Vadas MA (1993) Transforming growth factor-beta inhibits E-selectin expression on human endothelial cells. J Immunol 150:4494–4503PubMedGoogle Scholar
  58. 58.
    Hurwitz AA, Lyman WD, Berman JW (1995) Tumor necrosis factor a and transforming growth factor β up-regulate astrocyte expression of monocyte chemoattractant protein-1. J Neuroimmunol 57:193–198PubMedCrossRefGoogle Scholar
  59. 59.
    Luster AD (1998) Chemokines. Chemotactic cytokines that mediate inflammation. N Engl J Med 338:436–445PubMedCrossRefGoogle Scholar
  60. 60.
    Carr MW, Roth SJ, Luther E, Rose SS, Springer TA (1994) Monocyte chemoattractant protein 1 acts as a T-lymphocyte chemoattractant. Proc Natl Acad Sci USA 91:3652–3656PubMedCrossRefGoogle Scholar
  61. 61.
    Allavena P, Bianchi G, Zhou D, van Damme J, Jilek P, Sozzani S, Mantovani A (1994) Induction of natural killer cell migration by monocyte chemotactic protein-1, -2 and-3. Eur J Immunol 24:3233–3236PubMedCrossRefGoogle Scholar
  62. 62.
    Taub DD, Conlon K, Lloyd AR, Oppenheim JJ, Kelvin DJ (1993) Preferential migration of activated CD4+ and CD8+ T cells in response to MlP-lα and MlP-lβ. Science 260:355–358PubMedCrossRefGoogle Scholar
  63. 63.
    Adams EM, Kirkley J, Eidelman G, Dohlman J, Plötz PH (1997) The predominance of beta (CC) chemokine transcripts in idiopathic inflammatory muscle diseases. Proc Assoc Am Physicians 109:275–285PubMedGoogle Scholar
  64. 64.
    Confalonieri P, Bernasconi P, Megna P, Galbiati S, Cornelio F, Mantegazza R (2000) Increased expression of β-chemokines in muscle of patients with inflammatory myopathies. J Neuropathol Exp Neurol 59:164–169PubMedGoogle Scholar
  65. 65.
    Liprandi A, BartoU C, Figarella-Branger D, PeUissier J-F, Lepidi H (1999) Local expression of monocyte chemoattractant protein-1 (MCP-1) in idiopathic inflammatory myopathies. Acta Neuropathol 97:642–648PubMedCrossRefGoogle Scholar
  66. 66.
    De Rossi M, Bernasconi P, Baggi F, de Waal Malefyt R, Mantegazza R (2000) Cytokines and chemokines are both expressed by human myoblasts: possible relevance for the immune pathogenesis of muscle inflammation. Int Immunol 12:1329–1335PubMedCrossRefGoogle Scholar
  67. 67.
    Sugiura T, Kawaguchi Y, Harigai M et al (2000) Increased CD40 expression on muscle cells of polymyositis and dermatomyositis: role of CD40-CD40 ligand interaction in IL-6, IL-8, IL-15, and monocyte chemoattractant protein-1 production. J Immunol 164:6593–6600PubMedGoogle Scholar
  68. 68.
    Birkedal-Hansen H (1995) Proteolytic remodeling of extracellular matrix. Curr Opin Cell Biol 7:728–735PubMedCrossRefGoogle Scholar
  69. 69.
    Goetzl EJ, Banda MJ, Leppert D (1996) Matrix metalloproteinases in immunity. J Immunol 156:1–4PubMedGoogle Scholar
  70. 70.
    Choi Y-C, Dalakas MC (2000) Expression of matrix metalloproteinases in the muscle of patients with inflammatory myopathies. Neurology 54:65–71PubMedCrossRefGoogle Scholar
  71. 71.
    Berke G (1994) The binding and lysis of target cells by cytotoxic lymphocytes: molecular and cellular aspects. Ann Rev Immunol 12:735–773CrossRefGoogle Scholar
  72. 72.
    Goebels N, Michaelis D, Engelhardt M et al (1996) Differential expression of perforin in muscle-infiltrating T cells in polymyositis and dermatomyositis. J Clin Invest 97:2905–2910PubMedCrossRefGoogle Scholar
  73. 73.
    Mantegazza R, Bernasconi P, Confalonieri P, Cornelio F (1997) Inflammatory myopathies and systemic disorders: a review of immunopathogenetic mechanisms and clinical features. J Neurol 244:277–287PubMedCrossRefGoogle Scholar
  74. 74.
    Orimo S, Koga R, Goto K et al (1994) Immunohistochemical analysis of perforin and granzyme a in inflammatory myopathies. Neuromusc Disord 4:219–226PubMedCrossRefGoogle Scholar
  75. 75.
    Behrens L, Bender A, Johnson MA, Hohlfeld R (1997) Cytotoxic mechanisms in inflammatory myopathies. Co-expression of Fas and protective Bcl-2 in muscle fibres and inflammatory cells. Brain 120:929–938PubMedCrossRefGoogle Scholar
  76. 76.
    Fyhr IM, Oldfors A (1998) Upregulation of Fas/Fas ligand in inclusion body myositis. Ann Neurol 43:127–130PubMedCrossRefGoogle Scholar
  77. 77.
    Schneider C, Gold R, Dalakas MC et al (1996) MHC class I-mediated cytotoxicity does not induce apoptosis in muscle fibers nor in inflammatory T cells: studies in patients with polymyositis, dermatomyositis, and inclusion body myositis. J Neuropathol Exp Neurol 55:1205–1209PubMedCrossRefGoogle Scholar
  78. 78.
    Spuler S, Engel AG (1998) Unexpected sarcolemmal complement membrane attack complex deposits on nonnecrotic muscle fibers in muscular dystrophies. Neurology 50:41–46PubMedCrossRefGoogle Scholar
  79. 79.
    Askanas VA, Engel WK, Alvarez RB (1998) Fourteen newly recognized proteins at the human neuromuscular junctions and their nonjunctional accumulation in inclusion-body myositis. Ann N Y Acad Sci 841:28–56PubMedCrossRefGoogle Scholar
  80. 80.
    Li M, Dalakas MC (2000) The muscle mitogen-activated protein kinase is altered in sporadic inclusion body myositis. Neurology 54:1665–1669PubMedCrossRefGoogle Scholar
  81. 81.
    Medsger TA, Dawson WN, Masi AT (1970) The epidemiology of polymyositis. Am J Med 48:715–723PubMedCrossRefGoogle Scholar
  82. 82.
    Amato AA, Barohn RJ (2000) Evaluation and treatment of the idiopathic inflammatory myopathies. Neurologist 6:267–287CrossRefGoogle Scholar
  83. 83.
    Oldfors A, Lindberg C (1999) Inclusion body myositis. Curr Opin Neurol 12:527–533PubMedCrossRefGoogle Scholar
  84. 84.
    Koffman BM, Rugiero M, Dalakas MC (1998) Immune-mediated conditions and antibodies associated with sporadic inclusion body myositis. Muscle Nerve 21:115–117PubMedCrossRefGoogle Scholar
  85. 85.
    Hengstman GJ, van Engelen BG, Badrising UA, van de Hoogen FH, van Venrooij WJ (1998) Presence of the anti-Jo-1 autoantibody excludes inclusion body myositis. Ann Neurol 44:423PubMedCrossRefGoogle Scholar
  86. 86.
    Callen JP (2000) Dermatomyositis. Lancet 355:53–57PubMedCrossRefGoogle Scholar
  87. 87.
    Mastaglia FL (2000) Treatment of autoimmune inflammatory myopathies. Curr Opin Neurol 13:507–509PubMedCrossRefGoogle Scholar
  88. 88.
    Mantegazza R, Antozzi C, Cornelio F, Di Donato S (2001) Clinical trials in muscle disorders. In: Biller J, Bogousslavsky J (eds) Clinical trials in neurologic practice. Butterworth-Heinemann, Woburn, pp 311–325CrossRefGoogle Scholar
  89. 89.
    Griggs RC, Rose MR (1998) Evaluation of treatment for sporadic inclusion-body myositis. In: Askanas V, Serratrice G, Engel WK (eds) Inclusion-body myositis and myopathies. Cambridge University Press, Cambridge, pp 331–350Google Scholar
  90. 90.
    Dalakas MC, Koffman B, Fujii M, Spector S, Sivakumar K, Cupler E (2001) A controlled study of intravenous immunoglobulin combined with prednisone in the treatment of IBM. Neurology 56:323–327PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia 2002

Authors and Affiliations

  • R. Mantegazza
    • 1
  • P. Bernasconi
    • 1
  • F. Cornelio
    • 2
  1. 1.Myopathology and Immunology Unit, Department of Neuromuscular DiseasesNational Neurological Institute “Carlo Besta”MilanItaly
  2. 2.Department of Neuromuscular DiseasesNational Neurological Institute “Carlo Besta”MilanItaly

Personalised recommendations