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The Evolving Spectrum of Polymyositis and Dermatomyositis—Moving Towards Clinicoserological Syndromes: A Critical Review

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Abstract

The idiopathic inflammatory myopathies: polymyositis (PM) and dermatomyositis (DM) have been historically defined by broad clinical and pathological criteria. These conditions affect both adults and children with clinical features including muscle weakness, skin disease and internal organ involvement. Over the last few years, it has become increasingly apparent that using a clinico-serological approach, both DM and PM can be defined into more homogeneous subsets. A large number of antibodies are directed against cytoplasmic or nuclear components involved in key regulatory intra-cellular processes including protein synthesis, translocation and gene transcription within this disease spectrum. In addition, these autoantibodies are found in patients with clinical features other than myositis, in particular ‘idiopathic’ interstitial pneumonia emphasizing that these patients may in fact be a formes-frustes of autoimmune connective tissue disease. Other important findings are the identification of specific autoantibodies in both cancer-associated dermatomyositis, clinically amyopathic dermatomyositis and juvenile dermatomyositis, which previously were classically described as antibody-negative clinical subsets. Finally, work has highlighted how target autoantigens identified in the myositis-connective tissue disease overlap share common cellular mechanisms, which provides us with further insights into disease pathogenesis.

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References

  1. Bohan A, Peter JB (1975) Polymyositis and dermatomyositis (first of two parts). NEJM 292(7):344–7

    Article  CAS  PubMed  Google Scholar 

  2. Tanimoto K, Nakano K, Kano S, Mori S, Ueki H, Nishitani H et al (1995) Classification criteria for polymyositis and dermatomyositis. J Rheumatol 22(4):668–74

    CAS  PubMed  Google Scholar 

  3. Love LA, Leff RL, Fraser DD, Targoff IN, Dalakas M, Plotz PH et al (1991) A new approach to the classification of idiopathic inflammatory myopathy: myositis-specific autoantibodies define useful homogeneous patient groups. Medicine 70(6):360–74

    Article  CAS  PubMed  Google Scholar 

  4. Gunawardena H, Betteridge ZE, McHugh NJ (2009) Myositis-specific autoantibodies: their clinical and pathogenic significance in disease expression. Rheumatology 48(6):607–12

    Article  CAS  PubMed  Google Scholar 

  5. Friedman AW, Targoff IN, Arnett FC (1996) Interstitial lung disease with autoantibodies against aminoacyl-tRNA synthetases in the absence of clinically apparent myositis. Semin Arthritis Rheum 26(1):459–67

    Article  CAS  PubMed  Google Scholar 

  6. Kalluri M, Sahn SA, Oddis CV, Gharib SL, Christopher-Stine L, Danoff SK et al (2009) Clinical profile of anti-PL-12 autoantibody: cohort study and review of the literature. Chest 135(6):1550–6

    Article  CAS  PubMed  Google Scholar 

  7. Steen VD (2005) Autoantibodies in systemic sclerosis. Semin Arthritis Rheum 35(1):35–42

    Article  CAS  PubMed  Google Scholar 

  8. Lega J-C, Cottin V, Fabien N, Thivolet-Bejui F, Cordier J-F (2010) Interstitial lung disease associated with anti-PM/Scl or anti-aminoacyl-tRNA synthetase autoantibodies: a similar condition? J Rheumatol 37(5):1000–9

    Article  CAS  PubMed  Google Scholar 

  9. Ronnelid J, Barbasso Helmers S, Storfors H, Grip K, Ronnblom L, Franck-Larsson K et al (2009) Use of a commercial line blot assay as a screening test for autoantibodies in inflammatory myopathies. Autoimmun Rev 9(1):58–61

    Article  PubMed  Google Scholar 

  10. Fiorentino D, Chung L, Zwerner J, Rosen A, Casciola-Rosen L (2011) The mucocutaneous and systemic phenotype of dermatomyositis patients with antibodies to MDA5 (CADM-140): a retrospective study. J Am Acad Dermatol 65(1):25–34

    Article  PubMed Central  PubMed  Google Scholar 

  11. Hall JC, Casciola-Rosen L, Samedy L-A, Werner J, Owoyemi K, Danoff SK et al (2013) Anti-MDA5-associated dermatomyositis: Expanding the clinical spectrum. Arthritis Care Res (Hoboken) 65(8):1307–15

    Google Scholar 

  12. Labirua-Iturburu A, Selva-O'Callaghan A, Vincze M, Danko K, Vencovsky J, Fisher B et al (2012) Anti-PL-7 (anti-threonyl-tRNA synthetase) antisynthetase syndrome: clinical manifestations in a series of patients from a European multicenter study (EUMYONET) and review of the literature. Medicine 91(4):206–11

    Article  CAS  PubMed  Google Scholar 

  13. Gunawardena H, Robinson G, Betteridge ZE, Carmichael C, North J, Foley NM et al (2007) Serological associations and subtypes of diffuse parenchymal lung disease in scleroderma spectrum disorders and idiopathic inflammatory myopathy. Rheumatology 46(suppl 1):i76

    Google Scholar 

  14. Yamasaki Y, Yamada H, Nozaki T, Akaogi J, Nichols C, Lyons R et al (2006) Unusually high frequency of autoantibodies to PL-7 associated with milder muscle disease in Japanese patients with polymyositis/dermatomyositis. Arthritis Rheum 54(6):2004–9

    Article  CAS  PubMed  Google Scholar 

  15. Sato S, Kuwana M, Hirakata M (2007) Clinical characteristics of Japanese patients with anti-OJ (anti-isoleucyl-tRNA synthetase) autoantibodies. Rheumatology 46(5):842–5

    Article  CAS  PubMed  Google Scholar 

  16. Hervier B, Wallaert B, Hachulla E, Adoue D, Lauque D, Audrain M et al (2010) Clinical manifestations of anti-synthetase syndrome positive for anti-alanyl-tRNA synthetase (anti-PL12) antibodies: a retrospective study of 17 cases. Rheumatology 49(5):972–6

    Article  CAS  PubMed  Google Scholar 

  17. Hamaguchi Y, Fujimoto M, Matsushita T, Kaji K, Komura K, Hasegawa M et al (2013) Common and distinct clinical features in adult patients with anti-aminoacyl-tRNA synthetase antibodies: heterogeneity within the syndrome. Miller F, editor. PLoS ONE 8(4):e60442

    Google Scholar 

  18. Watanabe K, Handa T, Tanizawa K, Hosono Y, Taguchi Y, Noma S et al (2011) Detection of antisynthetase syndrome in patients with idiopathic interstitial pneumonias. Respir Med 105(8):1238–47

    Article  PubMed  Google Scholar 

  19. Aggarwal R, Cassidy E, Fertig N, Koontz DC, Lucas M, Ascherman DP et al (2013) Patients with non-Jo-1 anti-tRNA-synthetase autoantibodies have worse survival than Jo-1 positive patients. Ann Rheum Dis. doi:10.1136/annrheumdis-2012-201800

  20. Rutjes SA, Vree Egberts WTM, Jongen P, Van Den Hoogen F, Pruijn GJM, van Venrooij WJ (1997) Anti-Ro52 antibodies frequently co-occur with anti-Jo-1 antibodies in sera from patients with idiopathic inflammatory myopathy. Clin Exp Immunol 109:32–40

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Brouwer R, Hengstman GJD, Vree Egberts WTM, Ehrfeld H, Bozic B, Ghiradello A et al (2001) Autoantibody profiles in the sera of European patients with myositis. Ann Rheum Dis 60:116–23

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Schulte-Pelkum J, Fritzler M, Mahler M (2009) Latest update on the Ro/SS-A autoantibody system. Autoimmun Rev 8(7):632–7

    Article  CAS  PubMed  Google Scholar 

  23. Váncsa A, Csípő I, Németh J, Dévényi K, Gergely L, Dankó K (2009) Characteristics of interstitial lung disease in SS-A positive/Jo-1 positive inflammatory myopathy patients. Rheumatol Int 29(9):989–94

    Article  PubMed  Google Scholar 

  24. La Corte R, Lo Mo Naco A, Locaputo A, Dolzani F, Trotta F (2006) In patients with antisynthetase syndrome the occurrence of anti-Ro/SSA antibodies causes a more severe interstitial lung disease. Autoimmunity 39(3):249–53

    Article  PubMed  Google Scholar 

  25. Marie I, Hatron PY, Dominique S, Cherin P, Mouthon L, Menard JF et al (2012) Short-term and long-term outcome of anti-Jo1-positive patients with anti-Ro52 antibody. Semin Arthritis Rheu. Elsevier Inc, 41(6):890–9

    Google Scholar 

  26. Hudson M, Pope J, Mahler M, Tatibouet S, Steele R, Baron M et al (2012) Clinical significance of antibodies to Ro52/TRIM21 in systemic sclerosis. Arthritis Res Ther 14(2):R50

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Liang C, Needham M (2011) Necrotizing autoimmune myopathy. Curr Opin Rheumatol 23(6):612–9

    Article  PubMed  Google Scholar 

  28. Miller T, Al-Lozi MT, Lopate G, Pestronk A (2002) Myopathy with antibodies to the signal recognition particle: clinical and pathological features. J Neurol Neurosurg Psychiatry 73(4):420–8

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Suzuki S, Hayashi YK, Kuwana M, Tsuburaya R, Suzuki N, Nishino I (2012) Myopathy associated with antibodies to signal recognition particle: disease progression and neurological outcome. Arch Neurol 69(6):728–32

    PubMed  Google Scholar 

  30. Christopher-Stine L, Casciola-Rosen LA, Hong G, Chung T, Corse AM, Mammen AL (2010) A novel autoantibody recognizing 200-kd and 100-kd proteins is associated with an immune-mediated necrotizing myopathy. Arthritis Rheum 62(9):2757–66

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Mammen AL, Chung T, Christopher-Stine L, Rosen P, Rosen A, Doering KR et al (2011) Autoantibodies against 3-hydroxy-3-methylglutaryl-coenzyme A reductase in patients with statin-associated autoimmune myopathy. Arthritis Rheum 63(3):713–21

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Targoff IN, Reichlin M (1985) The association between Mi-2 antibodies and dermatomyositis. Arthritis Rheum 28(7):796–803

    Article  CAS  PubMed  Google Scholar 

  33. Targoff IN, Mamyrova G, Trieu EP, Perurena O, Koneru B, O'Hanlon TP et al (2006) A novel autoantibody to a 155-kd protein is associated with dermatomyositis. Arthritis Rheum 54(11):3682–9

    Article  CAS  PubMed  Google Scholar 

  34. Fujimoto M, Hamaguchi Y, Kaji K, Matsushita T, Ichimura Y, Kodera M et al (2012) Myositis-specific anti-155/140 autoantibodies target transcription intermediary factor 1 family proteins. Arthritis Rheum 64(2):513–22

    Article  CAS  PubMed  Google Scholar 

  35. Trallero-Araguás E, Rodrigo-Pendás JÁ, Selva-O'Callaghan A, Martínez-Gómez X, Bosch X, Labrador-Horrillo M et al (2012) Usefulness of anti-p155 autoantibody for diagnosing cancer-associated dermatomyositis: a systematic review and meta-analysis. Arthritis Rheum 64(2):523–32

    Article  PubMed  Google Scholar 

  36. Satoh M, Chan JY, Ross SJ, Li Y, Yamasaki Y, Yamada H et al (2012) Autoantibodies to transcription intermediary factor (TIF)1β associated with dermatomyositis. Arthritis Res Ther 14(2):R79

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. Dupont S, Mamidi A, Cordenonsi M, Montagner M, Zacchigna L, Adorno M et al (2009) FAM/USP9x, a deubiquitinating enzyme essential for TGFbeta signaling, controls Smad4 monoubiquitination. Cell 136(1):123–35

    Article  CAS  PubMed  Google Scholar 

  38. Andrieux G, Fattet L, Le Borgne M, Rimokh R, Théret N (2012) Dynamic regulation of Tgf-B signaling by Tif1γ: a computational approach. PLoS ONE 7(3):e33761, Chatterji D, editor

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  39. Gunawardena H, Wedderburn LR, North J, Betteridge Z, Dunphy J, Chinoy H et al (2007) Clinical associations of autoantibodies to a p155/140 kDa doublet protein in juvenile dermatomyositis. Rheumatology 47(3):324–8

    Article  Google Scholar 

  40. Bingham A, Mamyrova G, Rother KI, Oral E, Cochran E, Premkumar A et al (2008) Predictors of acquired lipodystrophy in juvenile-onset dermatomyositis and a gradient of severity. Medicine 87(2):70–86

    Article  PubMed Central  PubMed  Google Scholar 

  41. Betteridge Z, Gunawardena H, North J, Slinn J, McHugh N (2007) Identification of a novel autoantibody directed against small ubiquitin-like modifier activating enzyme in dermatomyositis. Arthritis Rheum 56(9):3132–7

    Article  CAS  PubMed  Google Scholar 

  42. Muro Y, Sugiura K, Akiyama M (2013) Low prevalence of anti-small ubiquitin-like modifier activating enzyme antibodies in dermatomyositis patients. Autoimmunity 46(4):279–84

    Article  CAS  PubMed  Google Scholar 

  43. Tarricone E, Ghirardello A, Rampudda M, Bassi N, Punzi L, Doria A (2012) Anti-SAE antibodies in autoimmune myositis: identification by unlabelled protein immunoprecipitation in an Italian patient cohort. J Immunol Methods 384(1–2):128–34

    Article  CAS  PubMed  Google Scholar 

  44. Betteridge ZE, Gunawardena H, Chinoy H, North J, Ollier WER, Cooper RG et al (2009) Clinical and human leucocyte antigen class II haplotype associations of autoantibodies to small ubiquitin-like modifier enzyme, a dermatomyositis-specific autoantigen target, in UK Caucasian adult-onset myositis. Ann Rheum Dis 68(10):1621–5

    Article  CAS  PubMed  Google Scholar 

  45. Sato S, Hoshino K, Satoh T, Fujita T, Kawakami Y, Fujita T et al (2009) 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(7):2193–200

    Article  CAS  PubMed  Google Scholar 

  46. Kobayashi I, Okura Y, Yamada H, PhD NKM, PhD MKM, PhD TAM (2011) Anti-melanoma differentiation-associated gene 5 antibody is a diagnostic and predictive marker for interstitial lung diseases associated with juvenile dermatomyositis. J Pediatr 158(4):675–7

    Article  CAS  PubMed  Google Scholar 

  47. Sato S, Kobayashi N, Yamazaki K, Suzuki Y. Clinical utility of anti-CADM-140/melanoma differentiation-associated gene 5 autoantibody titres in patients with juvenile dermatomyositis and rapidly progressive interstitial lung disease. American College of Rheumatology 76th Annual Meeting. Washington DC. 2012 Nov; Abstract 292:S128

  48. Betteridge ZE, Tansley S, Gunawardena H, Wedderburn LR, Chinoy H, Cooper RG et al. Adult and juvenile dermatomyositis patients with anti-MDA5 autoantibodies. Americal College of Rheumatology 76th Annual Meeting. Washington, DC. 2012 Nov; Abstract 1673:S715

  49. Gunawardena H, Wedderburn LR, Chinoy H, Betteridge ZE, North J, Ollier WER et al (2009) Autoantibodies to a 140-kd protein in juvenile dermatomyositis are associated with calcinosis. Arthritis Rheum 60(6):1807–14

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  50. Espada G, Maldonado Cocco J, Fertig N, Oddis CV (2009) Clinical and serologic characterization of an argentine pediatric myositis cohort: identification of a novel autoantibody (anti-MJ) to a 142-kDa protein. J Rheumatol 36:2457–551

    Article  Google Scholar 

  51. Ichimura Y, Matsushita T, Hamaguchi Y, Kaji K, Hasegawa M, Tanino Y et al (2013) Anti-NXP2 autoantibodies in adult patients with idiopathic inflammatory myopathies: possible association with malignancy. Ann Rheum Dis 71(5):710–3

    Article  Google Scholar 

  52. Ceribelli A, Fredi M, Taraborelli M, Cavazzana I, Franceschini F, Quinzanini M et al (2012) Anti-MJ/NXP-2 autoantibody specificity in a cohort of adult Italian patients with polymyositis/dermatomyositis. Arthritis Res Ther 14(2):R97

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  53. Gordon PA, Winer JB, Hoogendijk JE, Choy E (2012) Immunosuppressant and immunomodulatory treatment for dermatomyositis and polymyositis. The Cochrane Library. The Cochrane Collaboration (8):1–70

  54. Aggarwal R, Reed AM, Ascherman DP, Barohn RJ, Feldman BM, Miller FW et al. Clinical and serologic predictors of response in rituximab-treated refractory adult and juvenile dermatomyositis and polymyositis—the RIM Study. American College of Rheumatology 76th Annual Meeting. Washington, DC. 2012 Nov; S682

  55. Casciola-Rosen L (2005) Enhanced autoantigen expression in regenerating muscle cells in idiopathic inflammatory myopathy. J Exp Med 201(4):591–601

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  56. Takahashi K, Yoshida N, Murakami N, Kawata K, Ishizake H, Tanaka-Okamoto M et al (2007) Dynamic regulation of p53 subnuclear localization and senescence by MORC3. Mol Biol Cell 18:1701–9

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  57. Leff RL, Burgess SH, Miller FW, Love LA, Targoff IN, Dalakas MC et al (1991) Distinct seasonal patterns in the onset of adult idiopathic inflammatory myopathy in patients with anti-Jo-1 and anti-signal recognition particle autoantibodies. Arthritis Rheum 34(11):1391–6

    Article  CAS  PubMed  Google Scholar 

  58. Sarkar K, Weinberg CR, Oddis CV, Medsger TA Jr, Plotz PH, Reveille JD et al (2005) Seasonal influence on the onset of idiopathic inflammatory myopathies in serologically defined groups. Arthritis Rheum 52(8):2433–8

    Article  PubMed  Google Scholar 

  59. Shah M, Targoff IN, Rice MM, Miller FW, Rider LG, with the Childhood Myositis Heterogeneity Collaborative Study Group (2013) Ultraviolet radiation exposure is associated with clinical and autoantibody phenotypes in Juvenile Myositis. Arthritis Rheum 65(7):1934–41.

    Google Scholar 

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Acknowledgments

We would like to thank Juliet Dunphy (Bath Institute for Rheumatic Diseases, Bath, UK) for providing the images for Fig. 1 (ANA immunofluorescence patterns). We also thank and acknowledge Dr. Zoe Betteridge and Professor Neil McHugh for their continued support.

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Correspondence to Harsha Gunawardena.

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Tansley, S., Gunawardena, H. The Evolving Spectrum of Polymyositis and Dermatomyositis—Moving Towards Clinicoserological Syndromes: A Critical Review. Clinic Rev Allerg Immunol 47, 264–273 (2014). https://doi.org/10.1007/s12016-013-8387-6

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