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Pathogenesis, classification and treatment of inflammatory myopathies

Nature Reviews Rheumatology volume 7, pages 297–306 (2011)Cite this article

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Abstract

The inflammatory myopathies—collectively, myositis—are a heterogeneous group of chronic muscle disorders that differ in response to immunosuppressive treatment. Insufficient knowledge of the molecular pathways that drive pathogenesis (and underlie the clinical differences between subtypes) has hindered accurate classification, which in turn has been detrimental for clinical research. Nevertheless, new insights into pathogenesis are paving the way for improvements in diagnosis, classification and treatment. Accumulating data suggest that both immune and nonimmune mechanisms cause muscle weakness. Phenotyping of the T cells that accumulate in muscle tissue has identified proinflammatory, apoptosis resistant and cytotoxic CD4+ and CD8+ CD28null populations. Several myositis-specific autoantibodies have been identified, associated with distinct clinical phenotypes. Thus, adaptive immunity is involved in pathogenesis, and both T and B cells are interesting targets for therapy. Furthermore, genotyping has revealed activation of the type I interferon pathway in patients with dermatomyositis or with expression of particular autoantibodies. Decreased release of Ca2+ from the sarcoplasmic reticulum, as a consequence of release of proinflammatory cytokines and high mobility group protein B1, might contribute to muscle weakness, and nonimmune mechanisms potentially include a role for endoplasmic reticulum stress, autophagy and hypoxia. Deeper understanding, careful phenotyping of patients—and new classification criteria—will expedite clinical research.

Key Points

  • Myositis is a heterogeneous group of chronic inflammatory muscle disorders, the origins of which are not yet clear and for which efficient treatment is largely lacking

  • Recent findings suggest that both immune and nonimmune mechanisms are involved in the pathogenesis of myositis, and that different molecular pathways might predominate in different subsets of myositis

  • The immune mechanisms involve immune cells—T cells, B cells, dendritic cells and macrophages—and their products, such as cytokines and antibodies

  • Myositis-specific autoantibodies are helpful in the diagnosis of myositis, they identify different clinical subsets of myositis, and they might be important for differentiating pathogenic mechanisms between patients with myositis

  • Among nonimmune pathogenic mechanisms, there seem to be roles for endoplasmic reticulum stress, hypoxia and autophagy, contributing to the cause of muscle weakness

  • New classification criteria are needed to identify more homogenous subsets of patients, and subsets that are likely to share molecular pathways

  • Studying the outcomes of targeted therapies will facilitate understanding of disease mechanisms

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Figure 1: Potential immune mechanisms in myositis pathogenesis.
Figure 2: Localization of MHC class I antigens in muscle tissue of a patient with myositis.
Figure 3: Potential nonimmune mechanisms in myositis pathogenesis.

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References

  1. Dalakas, M. C. Polymyositis, dermatomyositis and inclusion-body myositis. N. Engl. J. Med. 325, 1487–1498 (1991).

    Article  CAS  PubMed  Google Scholar 

  2. Dalakas, M. C. & Hohlfeld, R. Polymyositis and dermatomyositis. Lancet 362, 971–982 (2003).

    Article  CAS  PubMed  Google Scholar 

  3. Plotz, P. H. et al. Current concepts in the idiopathic inflammatory myopathies: polymyositis, dermatomyositis, and related disorders. Ann. Intern. Med. 111, 143–157 (1989).

    Article  CAS  PubMed  Google Scholar 

  4. Li, C. K. et al. Overexpression of MHC class I heavy chain protein in young skeletal muscle leads to severe myositis: implications for juvenile myositis. Am. J. Pathol. 175, 1030–1040 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Nagaraju, K. et al. Activation of the endoplasmic reticulum stress response in autoimmune myositis: potential role in muscle fiber damage and dysfunction. Arthritis Rheum. 52, 1824–1835 (2005).

    Article  CAS  PubMed  Google Scholar 

  6. Askanas, V. & Engel, W. K. Inclusion-body myositis: a myodegenerative conformational disorder associated with Aβ, protein misfolding, and proteasome inhibition. Neurology 66, S39–S48 (2006).

    Article  CAS  PubMed  Google Scholar 

  7. Greenberg, S. A. How citation distortions create unfounded authority: analysis of a citation network. BMJ 339, b2680 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  8. Christopher-Stine, L. et al. A novel autoantibody recognizing 200-kd and 100-kd proteins is associated with an immune-mediated necrotizing myopathy. Arthritis Rheum. 62, 2757–2766 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Hengstman, G. J. et al. Anti-signal recognition particle autoantibodies: marker of a necrotising myopathy. Ann. Rheum. Dis. 65, 1635–1638 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. de Padilla, C. M. & Reed, A. M. Dendritic cells and the immunopathogenesis of idiopathic inflammatory myopathies. Curr. Opin. Rheumatol. 20, 669–674 (2008).

    Article  CAS  PubMed  Google Scholar 

  11. Reed, A. M. & Ernste, F. The inflammatory milieu in idiopathic inflammatory myositis. Curr. Rheumatol. Rep. 11, 295–301 (2009).

    Article  PubMed  Google Scholar 

  12. Szodoray, P. et al. Idiopathic inflammatory myopathies, signified by distinctive peripheral cytokines, chemokines and the TNF family members B-cell activating factor and a proliferation inducing ligand. Rheumatology (Oxford) 49, 1867–1877 (2010).

    Article  CAS  Google Scholar 

  13. Englund, P., Lindroos, E., Nennesmo, I., Klareskog, L. & Lundberg, I. E. Skeletal muscle fibers express major histocompatibility complex class II antigens independently of inflammatory infiltrates in inflammatory myopathies. Am. J. Pathol. 159, 1263–1273 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Behrens, L. et al. 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, 5943–5951 (1998).

    CAS  PubMed  Google Scholar 

  15. Hofbauer, M. et al. Clonal tracking of autoaggressive T cells in polymyositis by combining laser microdissection, single-cell PCR, and CDR3-spectratype analysis. Proc. Natl Acad. Sci. USA 100, 4090–4095 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Fasth, A. E. et al. T cell infiltrates in the muscles of patients with dermatomyositis and polymyositis are dominated by CD28null T cells. J. Immunol. 183, 4792–4799 (2009).

    Article  CAS  PubMed  Google Scholar 

  17. Pandya, J. M. et al. Expanded TCR-Vβ restricted T cells from sporadic inclusion body myositis patients are proinflammatory and cytotoxic CD28(null) T cells. Arthritis Rheum. 62, 3457–3466 (2010).

    Article  CAS  PubMed  Google Scholar 

  18. Fasth, A. E., Bjorkstrom, N. K., Anthoni, M., Malmberg, K. J. & Malmstrom, V. Activating NK-cell receptors co-stimulate CD4(+)CD28(–) T cells in patients with rheumatoid arthritis. Eur. J. Immunol. 40, 378–387 (2010).

    Article  CAS  PubMed  Google Scholar 

  19. Bettelli, E., Korn, T., Oukka, M. & Kuchroo, V. K. Induction and effector functions of T(H)17 cells. Nature 453, 1051–1057 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Page, G. et al. Plasma cell-like morphology of Th1-cytokine-producing cells associated with the loss of CD3 expression. Am. J. Pathol. 164, 409–417 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Chevrel, G. et al. Interleukin-17 increases the effects of IL-1β on muscle cells: arguments for the role of T cells in the pathogenesis of myositis. J. Neuroimmunol. 137, 125–133 (2003).

    Article  CAS  PubMed  Google Scholar 

  22. Waschbisch, A., Schwab, N., Ruck, T., Stenner, M. P. & Wiendl, H. FOXP3+ T regulatory cells in idiopathic inflammatory myopathies. J. Neuroimmunol. 225, 137–142 (2010).

    Article  CAS  PubMed  Google Scholar 

  23. Banica, L. et al. Quantification and molecular characterization of regulatory T cells in connective tissue diseases. Autoimmunity 42, 41–49 (2009).

    Article  CAS  PubMed  Google Scholar 

  24. Greenberg, S. A. et al. Plasma cells in muscle in inclusion body myositis and polymyositis. Neurology 65, 1782–1787 (2005).

    Article  CAS  PubMed  Google Scholar 

  25. De Bleecker, J. L., Engel, A. G. & Butcher, E. C. Peripheral lymphoid tissue-like adhesion molecule expression in nodular infiltrates in inflammatory myopathies. Neuromuscul. Disord. 6, 255–260 (1996).

    Article  CAS  PubMed  Google Scholar 

  26. Bradshaw, E. M. et al. A local antigen-driven humoral response is present in the inflammatory myopathies. J. Immunol. 178, 547–556 (2007).

    Article  CAS  PubMed  Google Scholar 

  27. Levine, T. D. Rituximab in the treatment of dermatomyositis: an open-label pilot study. Arthritis Rheum. 52, 601–607 (2005).

    Article  CAS  PubMed  Google Scholar 

  28. Majmudar, S., Hall, H. A. & Zimmermann, B. Treatment of adult inflammatory myositis with rituximab: an emerging therapy for refractory patients. J. Clin. Rheumatol. 15, 338–340 (2009).

    Article  PubMed  Google Scholar 

  29. Rios Fernandez, R., Callejas Rubio, J. L., Sanchez Cano, D., Saez Moreno, J. A. & Ortego Centeno, N. Rituximab in the treatment of dermatomyositis and other inflammatory myopathies. A report of 4 cases and review of the literature. Clin. Exp. Rheumatol. 27, 1009–1016 (2009).

    CAS  PubMed  Google Scholar 

  30. Tournadre, A. et al. Polymyositis and pemphigus vulgaris in a patient: successful treatment with rituximab. Joint Bone Spine 75, 728–729 (2008).

    Article  PubMed  Google Scholar 

  31. Vandenbroucke, E. et al. Rituximab in life threatening antisynthetase syndrome. Rheumatol. Int. 29, 1499–1502 (2009).

    Article  CAS  PubMed  Google Scholar 

  32. Page, G., Chevrel, G. & Miossec, P. Anatomic localization of immature and mature dendritic cell subsets in dermatomyositis and polymyositis: interaction with chemokines and Th1 cytokine-producing cells. Arthritis Rheum. 50, 199–208 (2004).

    Article  CAS  PubMed  Google Scholar 

  33. Eloranta, M. L. et al. A possible mechanism for endogenous activation of the type I interferon system in myositis patients with anti-Jo-1 or anti-Ro 52/anti-Ro 60 autoantibodies. Arthritis Rheum. 56, 3112–3124 (2007).

    Article  CAS  PubMed  Google Scholar 

  34. Greenberg, S. A. et al. Interferon α/β-mediated innate immune mechanisms in dermatomyositis. Ann. Neurol. 57, 664–678 (2005).

    Article  CAS  PubMed  Google Scholar 

  35. McNiff, J. M. & Kaplan, D. H. Plasmacytoid dendritic cells are present in cutaneous dermatomyositis lesions in a pattern distinct from lupus erythematosus. J. Cutan. Pathol. 35, 452–456 (2008).

    Article  PubMed  Google Scholar 

  36. Civatte, M. et al. Expression of the β chemokines CCL3, CCL4, CCL5 and their receptors in idiopathic inflammatory myopathies. Neuropathol. Appl. Neurobiol. 31, 70–79 (2005).

    Article  CAS  PubMed  Google Scholar 

  37. Confalonieri, P. et al. Increased expression of β-chemokines in muscle of patients with inflammatory myopathies. J. Neuropathol. Exp. Neurol. 59, 164–169 (2000).

    Article  CAS  PubMed  Google Scholar 

  38. De Paepe, B. & De Bleecker, J. L. β-Chemokine receptor expression in idiopathic inflammatory myopathies. Muscle Nerve 31, 621–627 (2005).

    Article  CAS  PubMed  Google Scholar 

  39. Rostasy, K. M. et al. Monocyte/macrophage differentiation in dermatomyositis and polymyositis. Muscle Nerve 30, 225–230 (2004).

    Article  PubMed  Google Scholar 

  40. Stone, K. B. et al. Anti-Jo-1 antibody levels correlate with disease activity in idiopathic inflammatory myopathy. Arthritis Rheum. 56, 3125–3131 (2007).

    Article  CAS  PubMed  Google Scholar 

  41. Brouwer, R. et al. Autoantibody profiles in the sera of European patients with myositis. Ann. Rheum. Dis. 60, 116–123 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Mahouachi, R. et al. Antisynthetase syndrome [French]. Tunis Med. 86, 195–196 (2008).

    PubMed  Google Scholar 

  43. Jordan Greco, A. S., Métrailler, J. C. & Dayer, E. The antisynthetase syndrome: a cause of rapidly progressive interstitial lung disease. Rev. Med. Suisse 3, 2675–2676, 2679–2681 (2007).

    PubMed  Google Scholar 

  44. Gomard-Mennesson, E. et al. Clinical significance of anti-histidyl-tRNA synthetase (Jo1) autoantibodies. Ann. NY Acad. Sci. 1109, 414–420 (2007).

    Article  CAS  PubMed  Google Scholar 

  45. Genth, E. Inflammatory muscle diseases: dermatomyositis, polymyositis, and inclusion body myositis [German]. Internist (Berl.) 46, 1218–1232 (2005).

    Article  CAS  Google Scholar 

  46. Legout, L. et al. The antisynthetase syndrome: a subgroup of inflammatory myopathies not to be unrecognized [French]. Rev. Med. Interne 23, 273–282 (2002).

    Article  CAS  PubMed  Google Scholar 

  47. Mammen, A. L. et al. Expression of the dermatomyositis autoantigen Mi-2 in regenerating muscle. Arthritis Rheum. 60, 3784–3793 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Kaji, K. et al. Identification of a novel autoantibody reactive with 155 and 140 kDa nuclear proteins in patients with dermatomyositis: an association with malignancy. Rheumatology (Oxford) 46, 25–28 (2007).

    Article  CAS  Google Scholar 

  49. Targoff, I. N. et al. A novel autoantibody to a 155-kd protein is associated with dermatomyositis. Arthritis Rheum. 54, 3682–3689 (2006).

    Article  CAS  PubMed  Google Scholar 

  50. Sato, S. et al. RNA helicase encoded by melanoma differentiation-associated gene 5 is a major autoantigen in patients with clinically amyopathic dermatomyositis: association with rapidly progressive interstitial lung disease. Arthritis Rheum. 60, 2193–2200 (2009).

    Article  CAS  PubMed  Google Scholar 

  51. Levine, S. M. et al. Novel conformation of histidyl-transfer RNA synthetase in the lung: the target tissue in Jo-1 autoantibody-associated myositis. Arthritis Rheum. 56, 2729–2739 (2007).

    Article  CAS  PubMed  Google Scholar 

  52. Soejima, M. et al. Role of innate immunity in a model of histidyl-tRNA synthetase (Jo-1)-mediated myositis. Arthritis Rheum. (2010).

  53. Katsumata, Y. et al. Species-specific immune responses generated by histidyl-tRNA synthetase immunization are associated with muscle and lung inflammation. J. Autoimmun. 29, 174–186 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Lovgren, T. et al. Induction of interferon-α by immune complexes or liposomes containing systemic lupus erythematosus autoantigen- and Sjögren's syndrome autoantigen-associated RNA. Arthritis Rheum. 54, 1917–1927 (2006).

    Article  CAS  PubMed  Google Scholar 

  55. Barbasso Helmers, S. et al. Sera from anti-Jo-1-positive patients with polymyositis and interstitial lung disease induce expression of intercellular adhesion molecule 1 in human lung endothelial cells. Arthritis Rheum. 60, 2524–2530 (2009).

    Article  PubMed  Google Scholar 

  56. Grundtman, C. et al. Immunolocalization of interleukin-1 receptors in the sarcolemma and nuclei of skeletal muscle in patients with idiopathic inflammatory myopathies. Arthritis Rheum. 56, 674–687 (2007).

    Article  PubMed  Google Scholar 

  57. Lundberg, I., Ulfgren, A. K., Nyberg, P., Andersson, U. & Klareskog, L. Cytokine production in muscle tissue of patients with idiopathic inflammatory myopathies. Arthritis Rheum. 40, 865–874 (1997).

    Article  CAS  PubMed  Google Scholar 

  58. St. Pierre, B. A., Kasper, C. E. & Lindsey, A. M. Fatigue mechanisms in patients with cancer: effects of tumor necrosis factor and exercise on skeletal muscle. Oncol. Nurs. Forum 19, 419–425 (1992).

    CAS  PubMed  Google Scholar 

  59. Tateyama, M. et al. Expression of tumor necrosis factor-α in muscles of polymyositis. J. Neurol. Sci. 146, 45–51 (1997).

    Article  CAS  PubMed  Google Scholar 

  60. Krystufkova, O. et al. Increased serum levels of B cell activating factor (BAFF) in subsets of patients with idiopathic inflammatory myopathies. Ann. Rheum. Dis. 68, 836–843 (2009).

    Article  CAS  PubMed  Google Scholar 

  61. Walsh, R. J. et al. Type I interferon-inducible gene expression in blood is present and reflects disease activity in dermatomyositis and polymyositis. Arthritis Rheum. 56, 3784–3792 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Serrano, A. L., Baeza-Raja, B., Perdiguero, E., Jardi, M. & Munoz-Canoves, P. Interleukin-6 is an essential regulator of satellite cell-mediated skeletal muscle hypertrophy. Cell. Metab. 7, 33–44 (2008).

    Article  CAS  PubMed  Google Scholar 

  63. Scuderi, F., Mannella, F., Marino, M., Provenzano, C. & Bartoccioni, E. IL-6-deficient mice show impaired inflammatory response in a model of myosin-induced experimental myositis. J. Neuroimmunol 176, 9–15 (2006).

    Article  CAS  PubMed  Google Scholar 

  64. Sugiura, T. et al. Increased IL-15 production of muscle cells in polymyositis and dermatomyositis. Int. Immunol. 14, 917–924 (2002).

    Article  CAS  PubMed  Google Scholar 

  65. Suzuki, J. et al. Serum levels of interleukin 15 in patients with rheumatic diseases. J. Rheumatol. 28, 2389–2391 (2001).

    CAS  PubMed  Google Scholar 

  66. Chiu, W. K., Fann, M. & Weng, N. P. Generation and growth of CD28nullCD8+ memory T cells mediated by IL-15 and its induced cytokines. J. Immunol. 177, 7802–7810 (2006).

    Article  CAS  PubMed  Google Scholar 

  67. Furmanczyk, P. S. & Quinn, L. S. Interleukin-15 increases myosin accretion in human skeletal myogenic cultures. Cell Biol. Int. 27, 845–851 (2003).

    Article  CAS  PubMed  Google Scholar 

  68. Andersson, U. & Harris, H. E. The role of HMGB1 in the pathogenesis of rheumatic disease. Biochim. Biophys. Acta 1799, 141–148 (2010).

    Article  CAS  PubMed  Google Scholar 

  69. Kokkola, R. et al. Successful treatment of collagen-induced arthritis in mice and rats by targeting extracellular high mobility group box chromosomal protein 1 activity. Arthritis Rheum. 48, 2052–2058 (2003).

    Article  CAS  PubMed  Google Scholar 

  70. Jiang, W. & Pisetsky, D. S. Mechanisms of disease: the role of high-mobility group protein 1 in the pathogenesis of inflammatory arthritis. Nat. Clin. Pract. Rheumatol. 3, 52–58 (2007).

    Article  CAS  PubMed  Google Scholar 

  71. Ulfgren, A. K. et al. Down-regulation of the aberrant expression of the inflammation mediator high mobility group box chromosomal protein 1 in muscle tissue of patients with polymyositis and dermatomyositis treated with corticosteroids. Arthritis Rheum. 50, 1586–1594 (2004).

    Article  CAS  PubMed  Google Scholar 

  72. Grundtman, C. et al. Effects of HMGB1 on in vitro responses of isolated muscle fibers and functional aspects in skeletal muscles of idiopathic inflammatory myopathies. FASEB J. 24, 570–578 (2010).

    Article  CAS  PubMed  Google Scholar 

  73. Alexanderson, H. et al. Patients with idiopathic inflammatory myopathies have low muscle endurance rather than low muscle strength [abstract 823]. Arthritis Rheum. 60 (Suppl.), S307 (2009).

    Google Scholar 

  74. Emslie-Smith, A. M. & Engel, A. G. Microvascular changes in early and advanced dermatomyositis: a quantitative study. Ann. Neurol. 27, 343–356 (1990).

    Article  CAS  PubMed  Google Scholar 

  75. Estruch, R. et al. Microvascular changes in skeletal muscle in idiopathic inflammatory myopathy. Hum. Pathol. 23, 888–895 (1992).

    Article  CAS  PubMed  Google Scholar 

  76. Grundtman, C., Tham, E., Ulfgren, A. K. & Lundberg, I. E. Vascular endothelial growth factor is highly expressed in muscle tissue of patients with polymyositis and patients with dermatomyositis. Arthritis Rheum. 58, 3224–3238 (2008).

    Article  CAS  PubMed  Google Scholar 

  77. Probst-Cousin, S., Neundorfer, B. & Heuss, D. Microvasculopathic neuromuscular diseases: lessons from hypoxia-inducible factors. Neuromuscul. Disord. 20, 192–197 (2010).

    Article  PubMed  Google Scholar 

  78. Dastmalchi, M. et al. Effect of physical training on the proportion of slow-twitch type I muscle fibers, a novel nonimmune-mediated mechanism for muscle impairment in polymyositis or dermatomyositis. Arthritis Rheum. 57, 1303–1310 (2007).

    Article  PubMed  Google Scholar 

  79. Nader, G. A. et al. A longitudinal, integrated, clinical, histological and mRNA profiling study of resistance exercise in myositis. Mol. Med. 16, 455–464 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Park, J. H. et al. Use of magnetic resonance imaging and P-31 magnetic resonance spectroscopy to detect and quantify muscle dysfunction in the amyopathic and myopathic variants of dermatomyositis. Arthritis Rheum. 38, 68–77 (1995).

    Article  PubMed  Google Scholar 

  81. Hamada, T. et al. Extracellular high mobility group box chromosomal protein 1 is a coupling factor for hypoxia and inflammation in arthritis. Arthritis Rheum. 58, 2675–2685 (2008).

    Article  PubMed  Google Scholar 

  82. Kim, I., Xu, W. & Reed, J. C. Cell death and endoplasmic reticulum stress: disease relevance and therapeutic opportunities. Nat. Rev. Drug Discov. 7, 1013–1030 (2008).

    Article  CAS  PubMed  Google Scholar 

  83. Hosoi, T. & Ozawa, K. Endoplasmic reticulum stress in disease: mechanisms and therapeutic opportunities. Clin. Sci. (Lond.) 118, 19–29 (2010).

    Article  Google Scholar 

  84. Delaunay, A. et al. The ER-bound RING finger protein 5 (RNF5/RMA1) causes degenerative myopathy in transgenic mice and is deregulated in inclusion body myositis. PLoS ONE 3, e1609 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. van der Pas, J., Hengstman, G. J., ter Laak, H. J., Borm, G. F. & van Engelen, B. G. Diagnostic value of MHC class I staining in idiopathic inflammatory myopathies. J. Neurol. Neurosurg. Psychiatry 75, 136–139 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Salomonsson, S. et al. Upregulation of MHC class I in transgenic mice results in reduced force-generating capacity in slow-twitch muscle. Muscle Nerve 39, 674–682 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Henriques-Pons, A. & Nagaraju, K. Nonimmune mechanisms of muscle damage in myositis: role of the endoplasmic reticulum stress response and autophagy in the disease pathogenesis. Curr. Opin. Rheumatol. 21, 581–587 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  88. Askanas, V., Engel, W. K. & Nogalska, A. Inclusion body myositis: a degenerative muscle disease associated with intra-muscle fiber multi-protein aggregates, proteasome inhibition, endoplasmic reticulum stress and decreased lysosomal degradation. Brain Pathol. 19, 493–506 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Nagaraju, K. et al. The inhibition of apoptosis in myositis and in normal muscle cells. J. Immunol. 164, 5459–5465 (2000).

    Article  CAS  PubMed  Google Scholar 

  90. Shtifman, A. et al. Amyloid-β protein impairs Ca(2+) release and contractility in skeletal muscle. Neurobiol. Aging 31, 2080–2090 (2010).

    Article  CAS  PubMed  Google Scholar 

  91. Temiz, P., Weihl, C. C. & Pestronk, A. Inflammatory myopathies with mitochondrial pathology and protein aggregates. J. Neurol. Sci. 278, 25–29 (2009).

    Article  PubMed  Google Scholar 

  92. Nogalska, A., D'Agostino, C., Terracciano, C., Engel, W. K. & Askanas, V. Impaired autophagy in sporadic inclusion-body myositis and in endoplasmic reticulum stress-provoked cultured human muscle fibers. Am. J. Pathol. 177, 1377–1387 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Bohan, A. & Peter, J. B. Polymyositis and dermatomyositis (first of two parts). N. Engl. J. Med. 292, 344–347 (1975).

    Article  CAS  PubMed  Google Scholar 

  94. Tanimoto, K. et al. Classification criteria for polymyositis and dermatomyositis. J. Rheumatol. 22, 668–674 (1995).

    CAS  PubMed  Google Scholar 

  95. Hoogendijk, J. E. et al. 119th ENMC international workshop: trial design in adult idiopathic inflammatory myopathies, with the exception of inclusion body myositis, 10–12 October 2003, Naarden, The Netherlands. Neuromuscul. Disord. 14, 337–345 (2004).

    Article  PubMed  Google Scholar 

  96. Engel, A. G. & Arahata, K. Mononuclear cells in myopathies: quantitation of functionally distinct subsets, recognition of antigen-specific cell-mediated cytotoxicity in some diseases, and implications for the pathogenesis of the different inflammatory myopathies. Hum. Pathol. 17, 704–721 (1986).

    Article  CAS  PubMed  Google Scholar 

  97. Arahata, K. & Engel, A. G. Monoclonal antibody analysis of mononuclear cells in myopathies. III: Immunoelectron microscopy aspects of cell-mediated muscle fiber injury. Ann. Neurol. 19, 112–125 (1986).

    Article  CAS  PubMed  Google Scholar 

  98. National Institue of Environmental Health Sciences. International Myositis Assessment and Clinical Research (IMACS) [online], (2011).

  99. Dalakas, M. C. Immunotherapy of myositis: issues, concerns and future prospects. Nat. Rev. Rheumatol. 6, 129–137 (2010).

    Article  PubMed  Google Scholar 

  100. Vencovsky, J. et al. Cyclosporine A versus methotrexate in the treatment of polymyositis and dermatomyositis. Scand. J. Rheumatol. 29, 95–102 (2000).

    Article  CAS  PubMed  Google Scholar 

  101. Caramaschi, P., Volpe, A., Carletto, A., Bambara, L. M. & Biasi, D. Long-standing refractory polymyositis responding to mycophenolate mofetil: a case report and review of the literature. Clin. Rheumatol. 26, 1795–1796 (2007).

    Article  PubMed  Google Scholar 

  102. Gelber, A. C., Nousari, H. C. & Wigley, F. M. Mycophenolate mofetil in the treatment of severe skin manifestations of dermatomyositis: a series of 4 cases. J. Rheumatol 27, 1542–1545 (2000).

    CAS  PubMed  Google Scholar 

  103. López de la Osa, A., Sánchez Tapia, C., Arias Díaz, M. & Terrancle de Juan, I. Antisynthetase syndrome with good response to mycophenolate mofetil [Spanish]. Rev. Clin. Esp. 207, 269–270 (2007).

    Article  PubMed  Google Scholar 

  104. Dalakas, M. C. et al. A controlled trial of high-dose intravenous immune globulin infusions as treatment for dermatomyositis. N. Engl. J. Med. 329, 1993–2000 (1993).

    Article  CAS  PubMed  Google Scholar 

  105. Barbasso Helmers, S. et al. Limited effects of high-dose intravenous immunoglobulin (IVIG) treatment on molecular expression in muscle tissue of patients with inflammatory myopathies. Ann. Rheum. Dis. 66, 1276–1283 (2007).

    Article  CAS  PubMed  Google Scholar 

  106. Wilkes, M. R., Sereika, S. M., Fertig, N., Lucas, M. R. & Oddis, C. V. Treatment of antisynthetase-associated interstitial lung disease with tacrolimus. Arthritis Rheum. 52, 2439–2446 (2005).

    Article  CAS  PubMed  Google Scholar 

  107. Haroon, M. & Devlin, J. Rituximab as a first-line agent for the treatment of dermatomyositis. Rheumatol. Int. doi:10.1007/S00296-010-1458-6.

  108. Furlan, A., Botsios, C., Ruffatti, A., Todesco, S. & Punzi, L. Antisynthetase syndrome with refractory polyarthritis and fever successfully treated with the IL-1 receptor antagonist, anakinra: A case report. Joint Bone Spine 75, 366–367 (2008).

    Article  PubMed  Google Scholar 

  109. Dorph, C. et al. Anakinra in patients with refractory idiopathic inflammatory myopathies [abstract 589]. Arthritis Rheum. 60 (Suppl.) S218 (2009).

    Google Scholar 

  110. Dastmalchi, M. et al. A high incidence of disease flares in an open pilot study of infliximab in patients with refractory inflammatory myopathies. Ann. Rheum. Dis. 67, 1670–1677 (2008).

    Article  CAS  PubMed  Google Scholar 

  111. Alexanderson, H. Exercise effects in patients with adult idiopathic inflammatory myopathies. Curr. Opin. Rheumatol. 21, 158–163 (2009).

    Article  PubMed  Google Scholar 

  112. Alexanderson, H., Dastmalchi, M., Esbjornsson-Liljedahl, M., Opava, C. H. & Lundberg, I. E. Benefits of intensive resistance training in patients with chronic polymyositis or dermatomyositis. Arthritis Rheum. 57, 768–777 (2007).

    Article  PubMed  Google Scholar 

  113. de Salles Painelli, V. et al. The possible role of physical exercise on the treatment of idiopathic inflammatory myopathies. Autoimmun. Rev. 8, 355–359 (2009).

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Medicine, Rheumatology Unit, Karolinska University Hospital, Solna, Karolinska Institutet, SE-171 76, Stockholm, Sweden

    Mei Zong & Ingrid E. Lundberg

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  1. Mei Zong
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  2. Ingrid E. Lundberg
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M. Zong and I. E. Lundberg contributed equally to all aspects of the preparation of this manuscript.

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Correspondence to Ingrid E. Lundberg.

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The authors declare no competing financial interests.

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Zong, M., Lundberg, I. Pathogenesis, classification and treatment of inflammatory myopathies. Nat Rev Rheumatol 7, 297–306 (2011). https://doi.org/10.1038/nrrheum.2011.39

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