Skip to main content
SpringerLink
Log in

Immunological Biomarkers in Dermatomyositis

  • Inflammatory Muscle Disease (R Aggarwal, Section Editor)
  • Published:
Current Rheumatology Reports Aims and scope Submit manuscript

Abstract

Dermatomyositis (DM) is a chronic acquired disorder that affects primarily the muscle and skin. The pathogenesis of DM, as well as methods for monitoring disease activity and predicting response to therapy, are subjects of active research. Studies looking to unveil the pathogenesis of DM have revealed key molecules that are potential biomarkers of disease activity. This article reviews briefly the recently discovered molecules that are candidate immunological biomarkers for diagnosing and monitoring disease activity in DM.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Nagaraju K, Lundberg IE. Polymyositis and dermatomyositis: pathophysiology. Rheum Dis Clin N Am. 2011;37:159–71. v.

    Article  Google Scholar 

  2. Plotz PH, Dalakas M, Leff RL, Love LA, Miller FW, Cronin ME. Current concepts in the idiopathic inflammatory myopathies: polymyositis, dermatomyositis, and related disorders. Ann Intern Med. 1989;111:143–57.

    Article  CAS  PubMed  Google Scholar 

  3. Sehgal PB, Wang L, Rayanade R, Pan H, Margulies L. Interleukin-6-type cytokines. Ann N Y Acad Sci. 1995;762:1–14.

    Article  CAS  PubMed  Google Scholar 

  4. Lundberg I, Ulfgren AK, Nyberg P, Andersson U, Klareskog L. Cytokine production in muscle tissue of patients with idiopathic inflammatory myopathies. Arthritis Rheum. 1997;40:865–74.

    Article  CAS  PubMed  Google Scholar 

  5. Bilgic H, Ytterberg SR, Amin S, McNallan KT, Wilson JC, Koeuth T, et al. Interleukin-6 and type I interferon-regulated genes and chemokines mark disease activity in dermatomyositis. Arthritis Rheum. 2009;60:3436–46.

    Article  CAS  PubMed  Google Scholar 

  6. Reed AM, Peterson E, Bilgic H, Ytterberg SR, Amin S, Hein MS, et al. Changes in novel biomarkers of disease activity in juvenile and adult dermatomyositis are sensitive biomarkers of disease course. Arthritis Rheum. 2012;64:4078–86. IL-6 expression in peripheral blood of patients with DM was assessed by performing multiplexed immunoassays. Serum IL-6 levels were significantly elevated in DM patients. Furthermore, the serum levels of IL-6 correlated with disease activity.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Gono T, Kaneko H, Kawaguchi Y, Hanaoka M, Kataoka S, Kuwana M, et al. Cytokine profiles in polymyositis and dermatomyositis complicated by rapidly progressive or chronic interstitial lung disease. Rheumatology. 2014;53:2196–203. Serum levels of IL-6 were evaluated in DM patients with interstitial lung disease (ILD) and compared them to the non-ILD subset. IL-6 levels were significantly higher in the ILD subset than the non-ILD subset.

    Article  PubMed  Google Scholar 

  8. Sugiura T, Kawaguchi Y, Harigai M, Takagi K, Ohta S, Fukasawa C, et al. 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. 2000;164:6593–600.

    Article  CAS  PubMed  Google Scholar 

  9. Chevrel G, Page G, Granet C, Streichenberger N, Varennes A, Miossec P. Interleukin-17 increases the effects of IL-1 beta on muscle cells: arguments for the role of T cells in the pathogenesis of myositis. J Neuroimmunol. 2003;137:125–33.

    Article  CAS  PubMed  Google Scholar 

  10. Shen H, Xia L, Lu J, Xiao W. Interleukin-17 and interleukin-23 in patients with polymyositis and dermatomyositis. Scand J Rheumatol. 2011;40:217–20.

    Article  CAS  PubMed  Google Scholar 

  11. Yuan L, Yao L, Zhao L, Xia L, Shen H, Lu J. Serum levels of soluble ST2 and interleukin-33 in patients with dermatomyositis and polymyositis. Clin Exp Rheumatol. 2013;31:428–32.

    PubMed  Google Scholar 

  12. Bellutti Enders F, van Wijk F, Scholman R, Hofer M, Prakken BJ, van Royen-Kerkhof A, et al. Correlation of CXCL10, tumor necrosis factor receptor type II, and galectin 9 with disease activity in juvenile dermatomyositis. Arthritis Rheum. 2014;66:2281–9. Serum levels of CXCL10 were increased in a juvenile DM cohort compared with the levels in healthy controls. Moreover, levels of CXCL10 were strongly correlated with the global VAS scores.

    Article  CAS  Google Scholar 

  13. Crescioli C, Sottili M, Bonini P, Cosmi L, Chiarugi P, Romagnani P, et al. Inflammatory response in human skeletal muscle cells: CXCL10 as a potential therapeutic target. Eur J Cell Biol. 2012;91:139–49.

    Article  CAS  PubMed  Google Scholar 

  14. Greenberg SA, Pinkus JL, Pinkus GS, Burleson T, Sanoudou D, Tawil R, et al. Interferon-alpha/beta-mediated innate immune mechanisms in dermatomyositis. Ann Neurol. 2005;57:664–78.

    Article  CAS  PubMed  Google Scholar 

  15. Cappelletti C, Baggi F, Zolezzi F, Biancolini D, Beretta O, Severa M, et al. Type I interferon and Toll-like receptor expression characterizes inflammatory myopathies. Neurology. 2011;76:2079–88.

    Article  CAS  PubMed  Google Scholar 

  16. Franzi S, Salajegheh M, Nazareno R, Greenberg SA. Type 1 interferons inhibit myotube formation independently of upregulation of interferon-stimulated gene 15. PLoS One. 2013;8, e65362.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Salajegheh M, Kong SW, Pinkus JL, Walsh RJ, Liao A, Nazareno R, et al. Interferon-stimulated gene 15 (ISG15) conjugates proteins in dermatomyositis muscle with perifascicular atrophy. Ann Neurol. 2010;67:53–63.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Niewold TB, Kariuki SN, Morgan GA, Shrestha S, Pachman LM. Elevated serum interferon-alpha activity in juvenile dermatomyositis: associations with disease activity at diagnosis and after thirty-six months of therapy. Arthritis Rheum. 2009;60:1815–24.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Dastmalchi M, Grundtman C, Alexanderson H, Mavragani CP, Einarsdottir H, Helmers SB, et al. A high incidence of disease flares in an open pilot study of infliximab in patients with refractory inflammatory myopathies. Ann Rheum Dis. 2008;67:1670–7.

    Article  CAS  PubMed  Google Scholar 

  20. Niewold TB, Wu SC, Smith M, Morgan GA, Pachman LM. Familial aggregation of autoimmune disease in juvenile dermatomyositis. Pediatrics. 2011;127:e1239–1246.

    Article  PubMed Central  PubMed  Google Scholar 

  21. Niewold TB, Kariuki SN, Morgan GA, Shrestha S, Pachman LM: Gene-gene-sex interaction in cytokine gene polymorphisms revealed by serum interferon alpha phenotype in juvenile dermatomyositis. J Pediatr 2010.

  22. Balboni I, Niewold TB, Morgan G, Limb C, Eloranta ML, Ronnblom L, Utz PJ, Pachman LM: Detection of anti-Ro, La, Smith and RNP autoantibodies by autoantigen microarray analysis and interferon-alpha induction in juvenile dermatomyositis. Arthritis and rheumatism 2013. High serum type I IFN in JDM patients was shown to be correlated with autoantibodies against RNA-binding proteins, explaining some of the heterogeneity between patients in circulating type I IFN.

  23. Liao AP, Salajegheh M, Nazareno R, Kagan JC, Jubin RG, Greenberg SA. Interferon beta is associated with type 1 interferon-inducible gene expression in dermatomyositis. Ann Rheum Dis. 2011;70:831–6.

    Article  CAS  PubMed  Google Scholar 

  24. Baechler EC, Bauer JW, Slattery CA, Ortmann WA, Espe KJ, Novitzke J, et al. An interferon signature in the peripheral blood of dermatomyositis patients is associated with disease activity. Mol Med. 2007;13:59–68.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Marie I, Mouthon L. Therapy of polymyositis and dermatomyositis. Autoimmun Rev. 2011;11:6–13.

    Article  CAS  PubMed  Google Scholar 

  26. Hengstman GJ, De Bleecker JL, Feist E, Vissing J, Denton CP, Manoussakis MN, et al. Open-label trial of anti-TNF-alpha in dermato- and polymyositis treated concomitantly with methotrexate. Eur Neurol. 2008;59:159–63.

    Article  CAS  PubMed  Google Scholar 

  27. Kobayashi J, Kitamura S. KL-6: a serum marker for interstitial pneumonia. Chest. 1995;108:311–5.

    Article  CAS  PubMed  Google Scholar 

  28. Kobayashi I, Ono S, Kawamura N, Okano M, Miyazawa K, Shibuya H, et al. KL-6 is a potential marker for interstitial lung disease associated with juvenile dermatomyositis. J Pediatr. 2001;138:274–6.

    Article  CAS  PubMed  Google Scholar 

  29. Kubo M, Ihn H, Yamane K, Kikuchi K, Yazawa N, Soma Y, et al. Serum KL-6 in adult patients with polymyositis and dermatomyositis. Rheumatology. 2000;39:632–6.

    Article  CAS  PubMed  Google Scholar 

  30. Krystufkova O, Vallerskog T, Helmers SB, Mann H, Putova I, Belacek J, et al. Increased serum levels of B cell activating factor (BAFF) in subsets of patients with idiopathic inflammatory myopathies. Ann Rheum Dis. 2009;68:836–43.

    Article  CAS  PubMed  Google Scholar 

  31. Peng QL, Shu XM, Wang DX, Wang Y, Lu X, Wang GC. B-cell activating factor as a serological biomarker for polymyositis and dermatomyositis. Biomark Med. 2014;8:395–403.

    Article  CAS  PubMed  Google Scholar 

  32. Lopez De Padilla CM, McNallan KT, Crowson CS, Bilgic H, Bram RJ, Hein MS, et al. BAFF expression correlates with idiopathic inflammatory myopathy disease activity measures and autoantibodies. J Rheum. 2013;40:294–302. They examined mRNA-expression levels of BAFF and their correlations with disease activity and found that BAFF mRNA levels of peripheral blood mononuclear cells correlated positively with disease activity measures in DM patients.

    Article  CAS  PubMed  Google Scholar 

  33. Filkova M, Hulejova H, Kuncova K, Plestilova L, Cerezo LA, Mann H, et al. Resistin in idiopathic inflammatory myopathies. Arthritis Res Ther. 2012;14:R111.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  34. Olazagasti JM, Hein M, Crowson CS, de Padilla CL, Peterson E, Baechler EC, et al. Adipokine gene expression in peripheral blood of adult and juvenile dermatomyositis patients and their relation to clinical parameters and disease activity measures. J Inflamm. 2015;12:29.

    Article  Google Scholar 

  35. Freret M, Drouot L, Obry A, Ahmed-Lacheheb S, Dauly C, Adriouch S, et al. Overexpression of MHC class I in muscle of lymphocyte-deficient mice causes a severe myopathy with induction of the unfolded protein response. Am J Pathol. 2013;183:893–904.

    Article  CAS  PubMed  Google Scholar 

  36. Nagaraju K, Casciola-Rosen L, Lundberg I, Rawat R, Cutting S, Thapliyal R, et al. Activation of the endoplasmic reticulum stress response in autoimmune myositis: potential role in muscle fiber damage and dysfunction. Arthritis Rheum. 2005;52:1824–35.

    Article  CAS  PubMed  Google Scholar 

  37. Nagaraju K, Raben N, Loeffler L, Parker T, Rochon PJ, Lee E, et al. Conditional up-regulation of MHC class I in skeletal muscle leads to self-sustaining autoimmune myositis and myositis-specific autoantibodies. Proc Natl Acad Sci U S A. 2000;97:9209–14.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  38. Sundaram C, Uppin MS, Meena AK. Major histocompatibility complex class I expression can be used as a diagnostic tool to differentiate idiopathic inflammatory myopathies from dystrophies. Neurol India. 2008;56:363–7.

    Article  CAS  PubMed  Google Scholar 

  39. Salaroli R, Baldin E, Papa V, Rinaldi R, Tarantino L, De Giorgi LB, et al. Validity of internal expression of the major histocompatibility complex class I in the diagnosis of inflammatory myopathies. J Clin Pathol. 2012;65:14–9.

    Article  PubMed  Google Scholar 

  40. Needham M, Fabian V, Knezevic W, Panegyres P, Zilko P, Mastaglia FL. Progressive myopathy with up-regulation of MHC-I associated with statin therapy. Neuromuscul Disord. 2007;17:194–200.

    Article  PubMed  Google Scholar 

  41. Rodriguez Cruz PM, Luo YB, Miller J, Junckerstorff RC, Mastaglia FL, Fabian V. An analysis of the sensitivity and specificity of MHC-I and MHC-II immunohistochemical staining in muscle biopsies for the diagnosis of inflammatory myopathies. Neuromuscul Disord : NMD. 2014;24:1025–35.

    Article  PubMed  Google Scholar 

  42. Santegoets KC, van Bon L, van den Berg WB, Wenink MH, Radstake TR. Toll-like receptors in rheumatic diseases: are we paying a high price for our defense against bugs? FEBS Lett. 2011;585:3660–6.

    Article  CAS  PubMed  Google Scholar 

  43. Kim GT, Cho ML, Park YE, Yoo WH, Kim JH, Oh HJ, et al. Expression of TLR2, TLR4, and TLR9 in dermatomyositis and polymyositis. Clin Rheumatol. 2010;29:273–9.

    Article  PubMed Central  PubMed  Google Scholar 

  44. Brunn A, Zornbach K, Hans VH, Haupt WF, Deckert M. Toll-like receptors promote inflammation in idiopathic inflammatory myopathies. J Neuropathol Exp Neurol. 2012;71:855–67.

    Article  CAS  PubMed  Google Scholar 

  45. Tournadre A, Lenief V, Miossec P. Expression of Toll-like receptor 3 and Toll-like receptor 7 in muscle is characteristic of inflammatory myopathy and is differentially regulated by Th1 and Th17 cytokines. Arthritis Rheum. 2010;62:2144–51.

    CAS  PubMed  Google Scholar 

Download references

Compliance with Ethics Guidelines

Conflict of Interest

Dr. Jeannette Olazagasti and Dr. Ann M. Reed have no conflict of interest. Dr. Timothy Niewold has received research grants from EMD Serono and Janssen, Inc.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Author information

Authors and Affiliations

  1. Division of Rheumatology, Mayo Clinic, 200 1st St SW, Rochester, MN, 55905, USA

    Jeannette M. Olazagasti

  2. Division of Rheumatology and Department of Immunology, Mayo Clinic, 200 1st St SW, Rochester, MN, 55905, USA

    Timothy B. Niewold

  3. Department of Pediatrics and Division of Rheumatology, Duke University School of Medicine, 201 Trent Drive, Durham, NC, 27710, USA

    Ann M. Reed

Authors
  1. Jeannette M. Olazagasti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Timothy B. Niewold
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ann M. Reed
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ann M. Reed.

Additional information

This article is part of the Topical Collection on Inflammatory Muscle Disease

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Olazagasti, J.M., Niewold, T.B. & Reed, A.M. Immunological Biomarkers in Dermatomyositis. Curr Rheumatol Rep 17, 68 (2015). https://doi.org/10.1007/s11926-015-0543-y

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11926-015-0543-y

Keywords

Search

Navigation