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Serum-soluble TRAIL: a potential biomarker for disease activity in myositis patients

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Abstract

Objectives

Tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) is a member of the TNF super-family, which is involved in the regulation of immune response and pathogenesis of autoimmune diseases, including polymyositis (PM) and dermatomyositis (DM). In this study, we examined the level and origin of serum-soluble TRAIL (sTRAIL) in patients with PM and DM and analyzed its association with disease activity and clinical features.

Method

11 PM patients, 33 DM patients, and 20 healthy controls were enrolled in this study. Clinical features were recorded when admitted, and disease activity was evaluated by myositis disease activity assessment visual analogue scale (MYOACT). TRAIL expression in muscle tissues was detected by immunohistochemistry. Serum sTRAIL levels were measured by enzyme-linked immunosorbent assay. The expression of membrane TRAIL (mTRAIL) and its receptors, including DR4 and DR5, on circulating T cells was analyzed by flow cytometry.

Results

TRAIL was expressed in infiltrated inflammatory cells in muscle tissues from patients. The serum sTRAIL level was markedly increased in patients and was positively correlated with the disease activity. Serum sTRAIL was decreased after therapy in patients and was specifically higher in patients with dysphagia, but lower in patients with autoantibody Jo-1 positive. The frequency of mTRAIL and its receptors on circulating T cells from patients were significantly elevated than that from healthy controls.

Conclusions

The serum sTRAIL could be a biomarker for evaluating the disease activity of PM and DM, and targeting the generation of TRAIL in T cells might be a potential approach in the treatment of PM and DM.

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References

  1. Dalakas MC, Hohlfeld R (2003) Polymyositis and dermatomyositis. Lancet 362(9388):971–982

    Article  CAS  PubMed  Google Scholar 

  2. Rider LG, Miller FW (2011) Deciphering the clinical presentations, pathogenesis, and treatment of the idiopathic inflammatory myopathies. JAMA 305(2):183–190

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Ceribelli A, De Santis M, Isailovic N, Gershwin ME, Selmi C (2017) The immune response and the pathogenesis of idiopathic inflammatory myositis: a critical review. Clin Rev Allergy Immunol 52(1):58–70

    Article  CAS  PubMed  Google Scholar 

  4. Dobloug C, Garen T, Bitter H, Stjärne J, Stenseth G, Grøvle L, Sem M, Gran JT, Molberg Ø (2015) Prevalence and clinical characteristics of adult polymyositis and dermatomyositis; data from a large and unselected Norwegian cohort. Ann Rheum Dis 74(8):1551–1556

    Article  PubMed  Google Scholar 

  5. Chevrel G, Page G, Miossec P (2006) Novel aspects on the contribution of T cells and dendritic cells in the pathogenesis of myositis. Autoimmunity 39(3):171–176

    Article  CAS  PubMed  Google Scholar 

  6. Wang S, El-Deiry WS (2003) TRAIL and apoptosis induction by TNF-family death receptors. Oncogene 22(53):8628–8633

    Article  CAS  PubMed  Google Scholar 

  7. LeBlanc HN, Ashkenazi A (2003) Apo2L/TRAIL and its death and decoy receptors. Cell Death Differ 10(1):66–75

    Article  CAS  PubMed  Google Scholar 

  8. Bouralexis S, Findlay DM, Evdokiou A (2005) Death to the bad guys: targeting cancer via Apo2L/TRAIL. Apoptosis 10(1):35–51

    Article  CAS  PubMed  Google Scholar 

  9. Martinez-Lostao L, Marzo I, Anel A, Naval J (2012) Targeting the Apo2L/TRAIL system for the therapy of autoimmune diseases and cancer. Biochem Pharmacol 83(11):1475–1483

    Article  CAS  PubMed  Google Scholar 

  10. Azab NA, Rady HM, Marzouk SA (2012) Elevated serum TRAIL levels in scleroderma patients and its possible association with pulmonary involvement. Clin Rheumatol 31(9):1359–1364

    Article  PubMed  Google Scholar 

  11. Lamhamedi-Cherradi SE, Zheng SJ, Maguschak KA, Peschon J, Chen YH (2003) Defective thymocyte apoptosis and accelerated autoimmune diseases in TRAIL−/− mice. Nat Immunol 4(3):255–260

    Article  CAS  PubMed  Google Scholar 

  12. Alger HM, Raben N, Pistilli E, Francia DL, Rawat R, Getnet D, Ghimbovschi S, Chen YW, Lundberg IE, Nagaraju K (2011) The role of TRAIL in mediating autophagy in myositis skeletal muscle: a potential nonimmune mechanism of muscle damage. Arthritis Rheum 63(11):3448–3457

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Zhao Y, Fedczyna TO, McVicker V, Caliendo J, Li H, Pachman LM (2007) Apoptosis in the skeletal muscle of untreated children with juvenile dermatomyositis: impact of duration of untreated disease. Clin Immunol 125(2):165–172

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Almasan A, Ashkenazi A (2003) Apo2L/TRAIL: apoptosis signaling, biology, and potential for cancer therapy. Cytokine Growth Factor Rev 14(3–4):337–348

    Article  CAS  PubMed  Google Scholar 

  15. Bohan A, Peter JB (1975) Polymyositis and dermatomyositis (first of two parts). N Engl J Med 292(7):344–347

    Article  CAS  PubMed  Google Scholar 

  16. Bohan A, Peter JB (1975) Polymyositis and dermatomyositis (second of two parts). N Engl J Med 292(8):403–407

    Article  CAS  Google Scholar 

  17. Isenberg DA, Allen E, Farewell V, Ehrenstein MR, Hanna MG, Lundberg IE, Oddis C, Pilkington C, Plotz P, Scott D, Vencovsky J, Cooper R, Rider L, Miller F, International Myositis and Clinical Studies Group (IMACS) (2004) International consensus outcome measures for patients with idiopathic inflammatory myopathies. Development and initial validation of myositis activity and damage indices in patients with adult onset disease. Rheumatology (Oxford) 43(1):49–54

    Article  CAS  Google Scholar 

  18. Shu XM, Lu X, Xie Y, Wang GC (2011) Clinical characteristics and favorable long-term outcomes for patients with idiopathic inflammatory myopathies: a retrospective single center study in China. BMC Neurol 11:143

    Article  PubMed  PubMed Central  Google Scholar 

  19. Lub-de Hooge MN, de Vries EG, de Jong S, Bijl M (2005) Soluble TRAIL concentrations are raised in patients with systemic lupus erythematosus. Ann Rheum Dis 64(6):854–858

    Article  CAS  PubMed  Google Scholar 

  20. Secchiero P, Corallini F, Castellino G, Bortoluzzi A, Caruso L, Bugatti S et al (2010) Baseline serum concentrations of TRAIL in early rheumatoid arthritis: relationship with response to disease-modifying antirheumatic drugs. J Rheumatol 37(7):1461–1466

    Article  CAS  PubMed  Google Scholar 

  21. Casciola-Rosen L, Nagaraju K, Plotz P, Wang K, Levine S, Gabrielson E, Corse A, Rosen A (2005) Enhanced autoantigen expression in regenerating muscle cells in idiopathic inflammatory myopathy. J Exp Med 201(4):591–601

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Aggarwal R, Cassidy E, Fertig N, Koontz DC, Lucas M, Ascherman DP, Oddis CV (2014) Patients with non-Jo-1 anti-tRNA-synthetase autoantibodies have worse survival than Jo-1 positive patients. Ann Rheum Dis 73(1):227–232

    Article  PubMed  Google Scholar 

  23. Tsai HF, Lai JJ, Chou AH, Wang TF, Wu CS, Hsu PN (2004) Induction of costimulation of human CD4 T cells by tumor necrosis factor-related apoptosis-inducing ligand: possible role in T cell activation in systemic lupus erythematosus. Arthritis Rheum 50(2):629–639

    Article  CAS  PubMed  Google Scholar 

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Funding

This study was supported by Research Foundation of Beijing Friendship Hospital, Capital Medical University (No. yyqdkt2016-9).

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Correspondence to Ting Duan.

Ethics declarations

The study was approved by the Ethics Committee of Beijing Friendship Hospital (approved number: 2018-P2-204-01). Informed consent was obtained from all enrolled participants for their data to be used for this study. Patients did not receive any financial compensation.

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Zhou, H., Wang, Y., Bi, K. et al. Serum-soluble TRAIL: a potential biomarker for disease activity in myositis patients. Clin Rheumatol 38, 1425–1431 (2019). https://doi.org/10.1007/s10067-018-04418-9

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  • DOI: https://doi.org/10.1007/s10067-018-04418-9

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