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The clinical utility of serum IL-35 in patients with polymyositis and dermatomyositis

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Abstract

The objectives of this study are to assess the levels of serum Interleukin-35 (IL-35) in patients with idiopathic inflammatory myopathies (IIMs) and to evaluate the association between IL-35 levels and IIM-related features. Serum IL-35 was detected in 76 patients with dermatomyositis (DM), 28 patients with polymyositis (PM), 98 disease controls (40 rheumatoid arthritis (RA), 34 systemic lupus erythematosus (SLE), 12 systemic sclerosis (SSc), and 12 sjogren syndrome (SS)), and 43 healthy controls by ELISA. Follow-up was conducted on 34 patients. Serum IL-35 was higher in myositis (PM/DM) patients than in healthy controls (median 76.6 pg/ml [interquartile range (IQR) 57.9–136.2] vs. 29.9 pg/ml (IQR 21.9–65.5), P < 0.001) and disease controls. Serum IL-35 in IIM patients negatively correlated with disease duration moderately (r = −0.35, P < 0.01). Patients with dysphagia had higher IL-35 than those without (median149.35 pg/ml (IQR 87.97–267.32) vs. 70.72 pg/ml (IQR 54.49–123.42), P = 0.001). Cross-sectional correlation analysis showed a weak positive correlation between serum IL-35 and CK (r = 0.293, P = 0.003), moderate positive correlation with erythrocyte sedimentation rate (ESR) (r = 0.304, P = 0.002), serum ferritin (SF) (r = 0.467, P = 0.001) and LDH levels (r = 0.401, P < 0.001). Additionally, serum IL-35 was higher in patients who were positive for anti-HMGCR (median 292.04 pg/ml (IQR 67.9–442.86) vs. 74.66 pg/ml (IQR 57.24–131.32), P = 0.038) and anti-SRP antibody (median 130.33 pg/ml (IQR 88.04–481.28) vs. 73.06 pg/ml (IQR 56.78–134.28), P = 0.009) than in negative patients, respectively. Follow-up study showed that changes in IL-35 levels after treatment correlated with changes in MYOACT scores moderately (r = 0.375, P = 0.029). These data indicate that increased serum IL-35 could act as a disease activity marker and as a risk factor for esophageal involvement in IIM. IL-35 may participate in the pathophysiological processes of IIM, but it still needs further study to confirm.

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References

  1. Dalakas MC (2015) Inflammatory muscle diseases. N Engl J Med 372:1734–1747

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  3. Dalakas MC (1991) Polymyositis, dermatomyositis and inclusion-body myositis. N Engl J Med 325:1487–1498

    Article  CAS  PubMed  Google Scholar 

  4. Mei Z, Lundberg IE (2011) Pathogenesis, classification and treatment of inflammatory myopathies. Nat Rev Rheumatol 7:297–306

    Article  Google Scholar 

  5. Lundberg IE (2000) The role of cytokines, chemokines, and adhesion molecules in the pathogenesis of idiopathic inflammatory myopathies. Curr Rheumatol Rep 2:216–224

    Article  CAS  PubMed  Google Scholar 

  6. Collison LW, Workman CJ, Kuo TT, et al. (2007) The inhibitory cytokine IL-35 contributes to regulatory T-cell function. Nature 450:566–569

    Article  CAS  PubMed  Google Scholar 

  7. Bardel E, Larousserie F, Charlot-Rabiega P, et al. (2008) Human CD4+CD25+Foxp3+ regulatory T cells do not constitutively express IL-35. J Immunol 181:6898–6905

    Article  CAS  PubMed  Google Scholar 

  8. Allan SE, Song-Zhao GX, Abraham T, et al. (2008) Inducible reprogramming of human T cells into Treg cells by a conditionally active form of FOXP3. Eur J Immunol 38:3282–3289

    Article  CAS  PubMed  Google Scholar 

  9. Collison LW, Chaturvedi V, Henderson AL, et al. (2010) IL-35-mediated induction of a potent regulatory T cell population. Nat Immunol 11:1093–1101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Filkova M, Vernerova Z, Hulejova H, et al. (2015) Pro-inflammatory effects of interleukin-35 in rheumatoid arthritis. Cytokine 73:36–43

    Article  CAS  PubMed  Google Scholar 

  11. Kuo J, Nardelli DT, Warner TF, et al. (2011) Interleukin-35 enhances Lyme arthritis in Borrelia-vaccinated and -infected mice. Clin Vaccine Immunol: CVI 18:1125–1132

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Thiolat A, Denys A, Petit M, et al. (2014) Interleukin-35 gene therapy exacerbates experimental rheumatoid arthritis in mice. Cytokine 69:87–93

    Article  CAS  PubMed  Google Scholar 

  13. Niedbala W, Wei XQ, Cai B, et al. (2007) IL-35 is a novel cytokine with therapeutic effects against collagen-induced arthritis through the expansion of regulatory T cells and suppression of Th17 cells. Eur J Immunol 37:3021–3029

    Article  CAS  PubMed  Google Scholar 

  14. Wang RX, Yu CR, Dambuza IM, et al. (2014) Interleukin-35 induces regulatory B cells that suppress autoimmune disease. Nat Med 20:633–641

    Article  PubMed  PubMed Central  Google Scholar 

  15. Bohan APJ (1975) Polymyositis and dermatomyositis (second of two parts). N Engl J Med 292:403–407

    Article  CAS  PubMed  Google Scholar 

  16. Bohan APJ (1975) Polymyositis and dermatomyositis (first of two parts). N Engl J Med 292:344–347

    Article  CAS  PubMed  Google Scholar 

  17. Isenberg DA, Allen E, Farewell V, et al. (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) 43:49–54

    Article  CAS  Google Scholar 

  18. Bettelli E, Korn T, Oukka M, et al. (2008) Induction and effector functions of T(H)17 cells. Nature 453:1051–1057

    Article  CAS  PubMed  Google Scholar 

  19. Llorente L, Zou W, Levy Y, et al. (1995) Role of interleukin 10 in the B lymphocyte hyperactivity and autoantibody production of human systemic lupus erythematosus. J Exp Med 181:839–844

    Article  CAS  PubMed  Google Scholar 

  20. Macneil IA, Suda T, Moore KW, et al. (1990) IL-10, a novel growth cofactor for mature and immature T cells. J Immunol 145:4167–4173

    CAS  PubMed  Google Scholar 

  21. Shachar I, Karin N (2013) The dual roles of inflammatory cytokines and chemokines in the regulation of autoimmune diseases and their clinical implications. J Leukoc Biol 93:51–61

    Article  CAS  PubMed  Google Scholar 

  22. Cai Z, Wong CK, Kam NW, et al. (2015) Aberrant expression of regulatory cytokine IL-35 in patients with systemic lupus erythematosus. Lupus 24

  23. Qiu F, Song L, Yang N, et al. (2013) Glucocorticoid downregulates expression of IL-12 family cytokines in systemic lupus erythematosus patients. Lupus 22:1011–1016

    Article  CAS  PubMed  Google Scholar 

  24. Banica L, Besliu A, Pistol G, et al. (2009) Quantification and molecular characterization of regulatory T cells in connective tissue diseases. Autoimmunity 42:41–49

    Article  CAS  PubMed  Google Scholar 

  25. Antiga E, Kretz CC, Klembt R, et al. (2010) Characterization of regulatory T cells in patients with dermatomyositis. J Autoimmun 35:342–350

    Article  CAS  PubMed  Google Scholar 

  26. Wang DX, Lu X, Zu N, et al. (2012) Clinical significance of peripheral blood lymphocyte subsets in patients with polymyositis and dermatomyositis. Clin Rheumatol 31:1691–1697

    Article  CAS  PubMed  Google Scholar 

  27. Nagaraju, Raben, Merritt, et al. (1998) A variety of cytokines and immunologically relevant surface molecules are expresssed by normal skeletal muscle cells under proinflammatory stimuli. Clin Exp Immunol 113:407–414

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Kempe S, Heinz P, Kokai E, et al. (2009) Epstein-barr virus-induced gene-3 is expressed in human atheroma plaques. Am J Pathol 175:440–447

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Seventer JMV, Nagai T, Seventer GAV (2002) Interferon-beta differentially regulates expression of the IL-12 family members p35, p40, p19 and EBI3 in activated human dendritic cells. J Neuroimmunol 133:60–71

    Article  PubMed  Google Scholar 

  30. Heidemann J, Rüther C, Kebschull M, et al. (2008) Expression of IL-12-related molecules in human intestinal microvascular endothelial cells is regulated by TLR3. Am J Physiol Gastrointest Liver Physiol 293:G1315–G1324

    Article  Google Scholar 

  31. Maaser C, Egan LJ, Birkenbach MP, et al. (2004) Expression of Epstein-Barr virus-induced gene 3 and other interleukin-12-related molecules by human intestinal epithelium. Immunology 112:437–445

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Xinyuan L, Jietang M, Anthony V, et al. (2012) IL-35 is a novel responsive anti-inflammatory cytokine—a new system of categorizing anti-inflammatory cytokines. PLoS One 7:65–65

    Google Scholar 

  33. Targoff IN, Johnson AE, Miller FW (1990) Antibody to signal recognition particle in polymyositis. Arthritis Rheum 33:1361–1370

    Article  CAS  PubMed  Google Scholar 

  34. Kao AH, David L, Mary L, et al. (2004) Anti-signal recognition particle autoantibody in patients with and patients without idiopathic inflammatory myopathy. Arthritis Rheum 50:209–215

    Article  CAS  PubMed  Google Scholar 

  35. Skowron W, Zemanek K, Wojdan K, et al. (2015) The effect of interleukin-35 on the integrity, ICAM-1 expression and apoptosis of human aortic smooth muscle cells. Pharmacol Rep: PR 67:376–381

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the National Natural Science Foundation of China (9154212181571603) and the Science and Technology Commission Foundation of Beijing (No:Z151100004015143).

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Authors and Affiliations

  1. Peking University China-Japan Friendship School of Clinical Medicine, No.2 Ying Hua East Road, Chao Yang District, Beijing, 100029, China

    Liguo Yin & Guochun Wang

  2. Department of Rheumatology, China-Japan Friendship Hospital, Ying Hua East Road, Chao Yang District, Beijing, 100029, China

    Yongpeng Ge, Hanbo Yang, Qinglin Peng, Xin Lu, Yamei Zhang & Guochun Wang

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  1. Liguo Yin
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  2. Yongpeng Ge
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Correspondence to Guochun Wang.

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Ethical approval for the research was obtained from the Research Review Committee (RRC) and the Ethical Review Committee (ERC) of the China-Japan Friendship Hospital.

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Yin, L., Ge, Y., Yang, H. et al. The clinical utility of serum IL-35 in patients with polymyositis and dermatomyositis. Clin Rheumatol 35, 2715–2721 (2016). https://doi.org/10.1007/s10067-016-3347-1

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  • DOI: https://doi.org/10.1007/s10067-016-3347-1

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