Skip to main content
Top
Published in: BMC Pulmonary Medicine 1/2020

01-12-2020 | Dermatomyositis | Research article

Serum levels of interleukins and S100A8/A9 correlate with clinical severity in patients with dermatomyositis-associated interstitial lung disease

Authors: Yueyan Lou, Yu Zheng, Bijun Fan, Liyan Zhang, Feng Zhu, Xiaodong Wang, Zhiwei Chen, Xiaoming Tan, Qing Wei

Published in: BMC Pulmonary Medicine | Issue 1/2020

Login to get access

Abstract

Background

Dermatomyositis (DM) is a systemic autoimmune inflammatory disorder that affects primarily skin, muscle and lung, frequently associated with interstitial lung disease (ILD). The objective of this study is to investigate the association between serum cytokines and clinical severity in patients with DM-ILD.

Methods

Serum samples of 30 healthy controls, 14 DM patients without ILD and 40 DM patients with ILD were collected. Serum S100A8/A9 levels were analyzed by enzyme-linked immunosorbent assay (ELISA) and levels of interleukins were measured by cytometric beads array (CBA). Then we performed multivariate logistic regression analysis to determine factors independently associated with ILD development.

Results

Serum IL-4, IL-6 and S100A8/A9 levels were significantly higher in DM patients with ILD than those in healthy controls (p = 0.0013, 0.0017 and < 0.0001, respectively). Serum IL-10 level of patients was dramatically lower than that in controls (p = 0.0001). In DM patients, the levels were significantly higher in patients with A/SIP than in those with CIP (p = 0.0046, 0.0339 and 0.0133) or without ILD (p = 0.0165, 0.0370 and < 0.0001). IL-4 (r = 0.1171, p = 0.0040), IL-6 (r = 0.1174, p = 0.0040) and IL-10 (r = − 0.1829, p = 0.0003) were significantly correlated with S100A8/A9 in DM-ILD patients. S100A8/A9 was significantly correlated with high-resolution computed tomography (HRCT) (r = 0.1642, p = 0.0157) and lung function (DLCO%: r = − 0.2066, p = 0.0061, FVC%: r = − 0.2156, p = 0.0050). Moreover, logistic regression analysis revealed that S100A8/A9 levels were independently associated with ILD development in DM patients (p = 0.004).

Conclusions

Serum level of S100A8/A9 may be a valuable predictor for assessing the clinical severity of DM-ILD patients. Serum IL-4, IL-6 and IL-10 levels were highly correlated with S100A8/A9, so these cytokines may play a synergistic effect on the progression of DM-ILD.
Literature
1.
go back to reference Lega JC, et al. Idiopathic inflammatory myopathies and the lung. Eur Respir Rev. 2015;24(136):216–38.PubMedCrossRef Lega JC, et al. Idiopathic inflammatory myopathies and the lung. Eur Respir Rev. 2015;24(136):216–38.PubMedCrossRef
2.
go back to reference Hallowell RW, Ascherman DP, Danoff SK. Pulmonary manifestations of polymyositis/dermatomyositis. Semin Respir Crit Care Med. 2014;35(2):239–48.PubMedCrossRef Hallowell RW, Ascherman DP, Danoff SK. Pulmonary manifestations of polymyositis/dermatomyositis. Semin Respir Crit Care Med. 2014;35(2):239–48.PubMedCrossRef
3.
go back to reference Hanaoka M, et al. KL-6 is a long-term disease-activity biomarker for interstitial lung disease associated with polymyositis/dermatomyositis, but is not a short-term disease-activity biomarker. Mod Rheumatol. 2018:1–20. Hanaoka M, et al. KL-6 is a long-term disease-activity biomarker for interstitial lung disease associated with polymyositis/dermatomyositis, but is not a short-term disease-activity biomarker. Mod Rheumatol. 2018:1–20.
4.
go back to reference Li L, et al. Myositis-specific autoantibodies in dermatomyositis/polymyositis with interstitial lung disease. J Neurol Sci. 2019;397:123–8.PubMedCrossRef Li L, et al. Myositis-specific autoantibodies in dermatomyositis/polymyositis with interstitial lung disease. J Neurol Sci. 2019;397:123–8.PubMedCrossRef
5.
go back to reference Morisset J, et al. Management of Myositis-Related Interstitial Lung Disease. Chest. 2016;150(5):1118–28.PubMedCrossRef Morisset J, et al. Management of Myositis-Related Interstitial Lung Disease. Chest. 2016;150(5):1118–28.PubMedCrossRef
6.
7.
go back to reference Moran EM, Mastaglia FL. The role of interleukin-17 in immune-mediated inflammatory myopathies and possible therapeutic implications. Neuromuscul Disord. 2014;24(11):943–52.PubMedCrossRef Moran EM, Mastaglia FL. The role of interleukin-17 in immune-mediated inflammatory myopathies and possible therapeutic implications. Neuromuscul Disord. 2014;24(11):943–52.PubMedCrossRef
8.
go back to reference Shimojima Y, et al. Phenotypes of peripheral blood lymphocytes and cytokine expression in Polymyositis and Dermatomyositis before treatment and after clinical remission. Clin Med Insights Arthritis Musculoskelet Disord. 2012;5:77–87.PubMedPubMedCentral Shimojima Y, et al. Phenotypes of peripheral blood lymphocytes and cytokine expression in Polymyositis and Dermatomyositis before treatment and after clinical remission. Clin Med Insights Arthritis Musculoskelet Disord. 2012;5:77–87.PubMedPubMedCentral
9.
go back to reference Giris M, et al. Elevated IL-4 and IFN-gamma levels in muscle tissue of patients with Dermatomyositis. Vivo. 2017;31(4):657–60.CrossRef Giris M, et al. Elevated IL-4 and IFN-gamma levels in muscle tissue of patients with Dermatomyositis. Vivo. 2017;31(4):657–60.CrossRef
10.
go back to reference Fujiyama T, et al. Preferential infiltration of interleukin-4-producing CXCR4+ T cells in the lesional muscle but not skin of patients with dermatomyositis. Clin Exp Immunol. 2014;177(1):110–20.PubMedPubMedCentralCrossRef Fujiyama T, et al. Preferential infiltration of interleukin-4-producing CXCR4+ T cells in the lesional muscle but not skin of patients with dermatomyositis. Clin Exp Immunol. 2014;177(1):110–20.PubMedPubMedCentralCrossRef
11.
go back to reference Rasheed Z, Akhtar N, Haqqi TM. Advanced glycation end products induce the expression of interleukin-6 and interleukin-8 by receptor for advanced glycation end product-mediated activation of mitogen-activated protein kinases and nuclear factor-kappaB in human osteoarthritis chondrocytes. Rheumatology (Oxford). 2011;50(5):838–51.CrossRef Rasheed Z, Akhtar N, Haqqi TM. Advanced glycation end products induce the expression of interleukin-6 and interleukin-8 by receptor for advanced glycation end product-mediated activation of mitogen-activated protein kinases and nuclear factor-kappaB in human osteoarthritis chondrocytes. Rheumatology (Oxford). 2011;50(5):838–51.CrossRef
12.
go back to reference Guloksuz SA, et al. Elevated plasma concentrations of S100 calcium-binding protein B and tumor necrosis factor alpha in children with autism spectrum disorders. Braz J Psychiatry. 2017;39(3):195–200.PubMedPubMedCentralCrossRef Guloksuz SA, et al. Elevated plasma concentrations of S100 calcium-binding protein B and tumor necrosis factor alpha in children with autism spectrum disorders. Braz J Psychiatry. 2017;39(3):195–200.PubMedPubMedCentralCrossRef
13.
go back to reference Roth J, et al. Phagocyte-specific S100 proteins: a novel group of proinflammatory molecules. Trends Immunol. 2003;24(4):155–8.PubMedCrossRef Roth J, et al. Phagocyte-specific S100 proteins: a novel group of proinflammatory molecules. Trends Immunol. 2003;24(4):155–8.PubMedCrossRef
14.
go back to reference Edgeworth J, et al. Identification of p8,14 as a highly abundant heterodimeric calcium binding protein complex of myeloid cells. J Biol Chem. 1991;266(12):7706–13.PubMedCrossRef Edgeworth J, et al. Identification of p8,14 as a highly abundant heterodimeric calcium binding protein complex of myeloid cells. J Biol Chem. 1991;266(12):7706–13.PubMedCrossRef
15.
go back to reference Raquil MA, et al. Blockade of antimicrobial proteins S100A8 and S100A9 inhibits phagocyte migration to the alveoli in streptococcal pneumonia. J Immunol. 2008;180(5):3366–74.PubMedCrossRef Raquil MA, et al. Blockade of antimicrobial proteins S100A8 and S100A9 inhibits phagocyte migration to the alveoli in streptococcal pneumonia. J Immunol. 2008;180(5):3366–74.PubMedCrossRef
16.
go back to reference Vogl T, et al. Mrp8 and Mrp14 are endogenous activators of toll-like receptor 4, promoting lethal, endotoxin-induced shock. Nat Med. 2007;13(9):1042–9.PubMedCrossRef Vogl T, et al. Mrp8 and Mrp14 are endogenous activators of toll-like receptor 4, promoting lethal, endotoxin-induced shock. Nat Med. 2007;13(9):1042–9.PubMedCrossRef
17.
go back to reference van Zoelen MA, et al. Expression and role of myeloid-related protein-14 in clinical and experimental sepsis. Am J Respir Crit Care Med. 2009;180(11):1098–106.PubMedCrossRef van Zoelen MA, et al. Expression and role of myeloid-related protein-14 in clinical and experimental sepsis. Am J Respir Crit Care Med. 2009;180(11):1098–106.PubMedCrossRef
18.
go back to reference Liang X, et al. Platelet-neutrophil interaction aggravates vascular in fl ammation and promotes the progression of atherosclerosis by activating the TLR4/NF-kappaB pathway. J Cell Biochem. 2019;120(4):5612–9.PubMedCrossRef Liang X, et al. Platelet-neutrophil interaction aggravates vascular in fl ammation and promotes the progression of atherosclerosis by activating the TLR4/NF-kappaB pathway. J Cell Biochem. 2019;120(4):5612–9.PubMedCrossRef
19.
go back to reference Nistala K, et al. Myeloid related protein induces muscle derived inflammatory mediators in juvenile dermatomyositis. Arthritis Res Ther. 2013;15(5):R131.PubMedPubMedCentralCrossRef Nistala K, et al. Myeloid related protein induces muscle derived inflammatory mediators in juvenile dermatomyositis. Arthritis Res Ther. 2013;15(5):R131.PubMedPubMedCentralCrossRef
20.
go back to reference Hesselstrand R, et al. Biomarkers from bronchoalveolar lavage fluid in systemic sclerosis patients with interstitial lung disease relate to severity of lung fibrosis. Respir Med. 2013;107(7):1079–86.PubMedCrossRef Hesselstrand R, et al. Biomarkers from bronchoalveolar lavage fluid in systemic sclerosis patients with interstitial lung disease relate to severity of lung fibrosis. Respir Med. 2013;107(7):1079–86.PubMedCrossRef
21.
go back to reference Yunchun L, et al. Clinical significance of myeloid-related protein 8/14 as a predictor for biological treatment and disease activity in rheumatoid arthritis. Ann Clin Lab Sci. 2018;48(1):63–8.PubMed Yunchun L, et al. Clinical significance of myeloid-related protein 8/14 as a predictor for biological treatment and disease activity in rheumatoid arthritis. Ann Clin Lab Sci. 2018;48(1):63–8.PubMed
22.
go back to reference Bohan A, Peter JB. Polymyositis and dermatomyositis (second of two parts). N Engl J Med. 1975;292(8):403–7.CrossRefPubMed Bohan A, Peter JB. Polymyositis and dermatomyositis (second of two parts). N Engl J Med. 1975;292(8):403–7.CrossRefPubMed
23.
go back to reference Bohan A, Peter JB. Polymyositis and dermatomyositis (first of two parts). N Engl J Med. 1975;292(7):344–7.PubMedCrossRef Bohan A, Peter JB. Polymyositis and dermatomyositis (first of two parts). N Engl J Med. 1975;292(7):344–7.PubMedCrossRef
24.
go back to reference American Thoracic Society. Idiopathic pulmonary fibrosis: diagnosis and treatment. International consensus statement. American Thoracic Society (ATS), and the European Respiratory Society (ERS). Am J Respir Crit Care Med. 2000;161(2 Pt 1):646–64. American Thoracic Society. Idiopathic pulmonary fibrosis: diagnosis and treatment. International consensus statement. American Thoracic Society (ATS), and the European Respiratory Society (ERS). Am J Respir Crit Care Med. 2000;161(2 Pt 1):646–64.
25.
go back to reference Ikezoe J, et al. High-resolution CT findings of lung disease in patients with polymyositis and dermatomyositis. J Thorac Imaging. 1996;11(4):250–9.PubMedCrossRef Ikezoe J, et al. High-resolution CT findings of lung disease in patients with polymyositis and dermatomyositis. J Thorac Imaging. 1996;11(4):250–9.PubMedCrossRef
27.
go back to reference Tyden H, et al. Pro-inflammatory S100 proteins are associated with glomerulonephritis and anti-dsDNA antibodies in systemic lupus erythematosus. Lupus. 2017;26(2):139–49.PubMedCrossRef Tyden H, et al. Pro-inflammatory S100 proteins are associated with glomerulonephritis and anti-dsDNA antibodies in systemic lupus erythematosus. Lupus. 2017;26(2):139–49.PubMedCrossRef
29.
go back to reference Andreasson K, et al. Faecal calprotectin: a biomarker of gastrointestinal disease in systemic sclerosis. J Intern Med. 2011;270(1):50–7.PubMedCrossRef Andreasson K, et al. Faecal calprotectin: a biomarker of gastrointestinal disease in systemic sclerosis. J Intern Med. 2011;270(1):50–7.PubMedCrossRef
30.
go back to reference Korthagen NM, et al. MRP14 is elevated in the bronchoalveolar lavage fluid of fibrosing interstitial lung diseases. Clin Exp Immunol. 2010;161(2):342–7.PubMedPubMedCentralCrossRef Korthagen NM, et al. MRP14 is elevated in the bronchoalveolar lavage fluid of fibrosing interstitial lung diseases. Clin Exp Immunol. 2010;161(2):342–7.PubMedPubMedCentralCrossRef
31.
go back to reference Bargagli E, et al. Macrophage-derived biomarkers of idiopathic pulmonary fibrosis. Pulm Med. 2011;2011:717130.PubMedCrossRef Bargagli E, et al. Macrophage-derived biomarkers of idiopathic pulmonary fibrosis. Pulm Med. 2011;2011:717130.PubMedCrossRef
32.
go back to reference Hara A, et al. S100A9 in BALF is a candidate biomarker of idiopathic pulmonary fibrosis. Respir Med. 2012;106(4):571–80.PubMedCrossRef Hara A, et al. S100A9 in BALF is a candidate biomarker of idiopathic pulmonary fibrosis. Respir Med. 2012;106(4):571–80.PubMedCrossRef
33.
34.
go back to reference Gono T, et al. Cytokine profiles in polymyositis and dermatomyositis complicated by rapidly progressive or chronic interstitial lung disease. Rheumatology (Oxford). 2014;53(12):2196–203.CrossRef Gono T, et al. Cytokine profiles in polymyositis and dermatomyositis complicated by rapidly progressive or chronic interstitial lung disease. Rheumatology (Oxford). 2014;53(12):2196–203.CrossRef
35.
go back to reference Gono T, et al. Interleukin-18 is a key mediator in dermatomyositis: potential contribution to development of interstitial lung disease. Rheumatology (Oxford). 2010;49(10):1878–81.CrossRef Gono T, et al. Interleukin-18 is a key mediator in dermatomyositis: potential contribution to development of interstitial lung disease. Rheumatology (Oxford). 2010;49(10):1878–81.CrossRef
36.
go back to reference Kawasumi H, et al. IL-6, IL-8, and IL-10 are associated with hyperferritinemia in rapidly progressive interstitial lung disease with polymyositis/dermatomyositis. Biomed Res Int. 2014;2014:815245.PubMedPubMedCentralCrossRef Kawasumi H, et al. IL-6, IL-8, and IL-10 are associated with hyperferritinemia in rapidly progressive interstitial lung disease with polymyositis/dermatomyositis. Biomed Res Int. 2014;2014:815245.PubMedPubMedCentralCrossRef
37.
go back to reference Reed AM, et al. Changes in novel biomarkers of disease activity in juvenile and adult dermatomyositis are sensitive biomarkers of disease course. Arthritis Rheum. 2012;64(12):4078–86.PubMedPubMedCentralCrossRef Reed AM, et al. Changes in novel biomarkers of disease activity in juvenile and adult dermatomyositis are sensitive biomarkers of disease course. Arthritis Rheum. 2012;64(12):4078–86.PubMedPubMedCentralCrossRef
38.
go back to reference Ouyang W, et al. Regulation and functions of the IL-10 family of cytokines in inflammation and disease. Annu Rev Immunol. 2011;29:71–109.PubMedCrossRef Ouyang W, et al. Regulation and functions of the IL-10 family of cytokines in inflammation and disease. Annu Rev Immunol. 2011;29:71–109.PubMedCrossRef
39.
go back to reference Gabrysova L, et al. C-Maf controls immune responses by regulating disease-specific gene networks and repressing IL-2 in CD4(+) T cells. Nat Immunol. 2018;19(5):497–507.PubMedPubMedCentralCrossRef Gabrysova L, et al. C-Maf controls immune responses by regulating disease-specific gene networks and repressing IL-2 in CD4(+) T cells. Nat Immunol. 2018;19(5):497–507.PubMedPubMedCentralCrossRef
40.
go back to reference Lin CC, et al. Bhlhe40 controls cytokine production by T cells and is essential for pathogenicity in autoimmune neuroinflammation. Nat Commun. 2014;5:3551.PubMedCrossRef Lin CC, et al. Bhlhe40 controls cytokine production by T cells and is essential for pathogenicity in autoimmune neuroinflammation. Nat Commun. 2014;5:3551.PubMedCrossRef
41.
go back to reference Marie I, et al. Short-term and long-term outcomes of interstitial lung disease in polymyositis and dermatomyositis: a series of 107 patients. Arthritis Rheum. 2011;63(11):3439–47.PubMedCrossRef Marie I, et al. Short-term and long-term outcomes of interstitial lung disease in polymyositis and dermatomyositis: a series of 107 patients. Arthritis Rheum. 2011;63(11):3439–47.PubMedCrossRef
42.
go back to reference Bonnefoy O, et al. Serial chest CT findings in interstitial lung disease associated with polymyositis-dermatomyositis. Eur J Radiol. 2004;49(3):235–44.PubMedCrossRef Bonnefoy O, et al. Serial chest CT findings in interstitial lung disease associated with polymyositis-dermatomyositis. Eur J Radiol. 2004;49(3):235–44.PubMedCrossRef
43.
go back to reference Ley B, Collard HR, King TE Jr. Clinical course and prediction of survival in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2011;183(4):431–40.PubMedCrossRef Ley B, Collard HR, King TE Jr. Clinical course and prediction of survival in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2011;183(4):431–40.PubMedCrossRef
Metadata
Title
Serum levels of interleukins and S100A8/A9 correlate with clinical severity in patients with dermatomyositis-associated interstitial lung disease
Authors
Yueyan Lou
Yu Zheng
Bijun Fan
Liyan Zhang
Feng Zhu
Xiaodong Wang
Zhiwei Chen
Xiaoming Tan
Qing Wei
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Pulmonary Medicine / Issue 1/2020
Electronic ISSN: 1471-2466
DOI
https://doi.org/10.1186/s12890-020-01226-3

Other articles of this Issue 1/2020

BMC Pulmonary Medicine 1/2020 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.