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Published in: Arthritis Research & Therapy 1/2017

Open Access 01-12-2017 | Research article

Clinical significance of soluble CD163 in polymyositis-related or dermatomyositis-related interstitial lung disease

Authors: Yasunori Enomoto, Yuzo Suzuki, Hironao Hozumi, Kazutaka Mori, Masato Kono, Masato Karayama, Kazuki Furuhashi, Tomoyuki Fujisawa, Noriyuki Enomoto, Yutaro Nakamura, Naoki Inui, Daisuke Suzuki, Noriyoshi Ogawa, Ran Nakashima, Tsuneyo Mimori, Toshihide Iwashita, Takafumi Suda

Published in: Arthritis Research & Therapy | Issue 1/2017

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Abstract

Background

Macrophage activation is involved in the pathogenesis of polymyositis (PM)/dermatomyositis (DM). CD163, a scavenger receptor expressed on the surface of activated macrophages, mediates anti-inflammatory functions. This study aimed to evaluate the clinical significance of soluble CD163 (sCD163) in PM/DM-related interstitial lung disease (ILD).

Methods

The main subjects were 48 patients with PM/DM-related ILD. As controls, 10 patients with PM/DM without ILD and 20 healthy volunteers were enrolled. In patients with PM/DM-related ILD, the baseline characteristics and clinical course were obtained through a review of patient medical records. Serum sCD163 levels at ILD diagnosis were quantified by enzyme-linked immunosorbent assay, which were compared with the other baseline clinical factors and evaluated for potential as a prognostic biomarker. In addition, immunohistochemistry analysis using anti-human CD163 antibody was performed on the lung sections of two patients with DM-related ILD (a survivor and non-survivor, respectively) and one patient with early-stage lung cancer as a normal control.

Results

The median value of serum sCD163 in patients with PM/DM-related ILD was 818 ng/mL, which was higher than that of PM/DM patients without ILD and healthy volunteers (716 ng/mL and 340 ng/mL, respectively). Significant but mild correlations with serum sCD163 levels were observed for serum C-reactive protein levels (r = 0.322) and % predicted forced vital capacity (r = −0.301) in patients with PM/DM-related ILD. A Cox proportional hazard model demonstrated that patients with PM/DM-related ILD and higher sCD163 levels had worse prognosis (age-adjusted and gender-adjusted hazard ratio per 100 ng/mL increase 1.27, 95% confidence interval 1.11–1.45, P <0.001). In immunohistochemistry analysis, compared with normal lung, alveolar infiltration of CD163-positive macrophages was evident in the lungs of patients with DM-related ILD. Especially, the finding was more severe in the non-survivor’s lung.

Conclusions

Serum sCD163 might be a potential biomarker for predicting the severity and prognosis of PM/DM-related ILD. Our results suggest the importance of macrophage activation in the disease.
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Literature
1.
go back to reference Ernste FC, Reed AM. Idiopathic inflammatory myopathies: current trends in pathogenesis, clinical features, and up-to-date treatment recommendations. Mayo Clin Proc. 2013;88:83–105.CrossRefPubMed Ernste FC, Reed AM. Idiopathic inflammatory myopathies: current trends in pathogenesis, clinical features, and up-to-date treatment recommendations. Mayo Clin Proc. 2013;88:83–105.CrossRefPubMed
2.
go back to reference Bohan A, Peter JB. Polymyositis and dermatomyositis (first of two parts). N Engl J Med. 1975;292:344–7.CrossRefPubMed Bohan A, Peter JB. Polymyositis and dermatomyositis (first of two parts). N Engl J Med. 1975;292:344–7.CrossRefPubMed
3.
go back to reference Mathai SC, Danoff SK. Management of interstitial lung disease associated with connective tissue disease. BMJ. 2016;352:h6819.CrossRefPubMed Mathai SC, Danoff SK. Management of interstitial lung disease associated with connective tissue disease. BMJ. 2016;352:h6819.CrossRefPubMed
4.
go back to reference Fujisawa T, Suda T, Nakamura Y, Enomoto N, Ide K, Toyoshima M, et al. Differences in clinical features and prognosis of interstitial lung diseases between polymyositis and dermatomyositis. J Rheumatol. 2005;32:58–64.PubMed Fujisawa T, Suda T, Nakamura Y, Enomoto N, Ide K, Toyoshima M, et al. Differences in clinical features and prognosis of interstitial lung diseases between polymyositis and dermatomyositis. J Rheumatol. 2005;32:58–64.PubMed
5.
go back to reference Suda T, Fujisawa T, Enomoto N, Nakamura Y, Inui N, Naito T, et al. Interstitial lung diseases associated with amyopathic dermatomyositis. Eur Respir J. 2006;28:1005–12.CrossRefPubMed Suda T, Fujisawa T, Enomoto N, Nakamura Y, Inui N, Naito T, et al. Interstitial lung diseases associated with amyopathic dermatomyositis. Eur Respir J. 2006;28:1005–12.CrossRefPubMed
6.
go back to reference Fujisawa T, Hozumi H, Kono M, Enomoto N, Hashimoto D, Nakamura Y, et al. Prognostic factors for myositis-associated interstitial lung disease. PLoS One. 2014;9:e98824.CrossRefPubMedPubMedCentral Fujisawa T, Hozumi H, Kono M, Enomoto N, Hashimoto D, Nakamura Y, et al. Prognostic factors for myositis-associated interstitial lung disease. PLoS One. 2014;9:e98824.CrossRefPubMedPubMedCentral
7.
go back to reference Hozumi H, Enomoto N, Kono M, Fujisawa T, Inui N, Nakamura Y, et al. Prognostic significance of anti-aminoacyl-tRNA synthetase antibodies in polymyositis/dermatomyositis-associated interstitial lung disease: a retrospective case control study. PLoS One. 2015;10:e0120313.CrossRefPubMedPubMedCentral Hozumi H, Enomoto N, Kono M, Fujisawa T, Inui N, Nakamura Y, et al. Prognostic significance of anti-aminoacyl-tRNA synthetase antibodies in polymyositis/dermatomyositis-associated interstitial lung disease: a retrospective case control study. PLoS One. 2015;10:e0120313.CrossRefPubMedPubMedCentral
8.
go back to reference Sasano H, Hagiwara E, Kitamura H, Enomoto Y, Matsuo N, Baba T, et al. Long-term clinical course of anti-glycyl tRNA synthetase (anti-EJ) antibody-related interstitial lung disease pathologically proven by surgical lung biopsy. BMC Pulm Med. 2016;16:168.CrossRefPubMedPubMedCentral Sasano H, Hagiwara E, Kitamura H, Enomoto Y, Matsuo N, Baba T, et al. Long-term clinical course of anti-glycyl tRNA synthetase (anti-EJ) antibody-related interstitial lung disease pathologically proven by surgical lung biopsy. BMC Pulm Med. 2016;16:168.CrossRefPubMedPubMedCentral
9.
go back to reference Fabriek BO, Dijkstra CD, van den Berg TK. The macrophage scavenger receptor CD163. Immunobiology. 2005;210:153–60.CrossRefPubMed Fabriek BO, Dijkstra CD, van den Berg TK. The macrophage scavenger receptor CD163. Immunobiology. 2005;210:153–60.CrossRefPubMed
10.
go back to reference Lau SK, Chu PG, Weiss LM. CD163: a specific marker of macrophages in paraffin-embedded tissue samples. Am J Clin Pathol. 2004;122:794–801.CrossRefPubMed Lau SK, Chu PG, Weiss LM. CD163: a specific marker of macrophages in paraffin-embedded tissue samples. Am J Clin Pathol. 2004;122:794–801.CrossRefPubMed
11.
12.
go back to reference Dorph C, Englund P, Nennesmo I, Lundberg IE. Signs of inflammation in both symptomatic and asymptomatic muscles from patients with polymyositis and dermatomyositis. Ann Rheum Dis. 2006;65:1565–71.CrossRefPubMedPubMedCentral Dorph C, Englund P, Nennesmo I, Lundberg IE. Signs of inflammation in both symptomatic and asymptomatic muscles from patients with polymyositis and dermatomyositis. Ann Rheum Dis. 2006;65:1565–71.CrossRefPubMedPubMedCentral
13.
go back to reference Peng QL, Zhang YL, Shu XM, Yang HB, Zhang L, Chen F, et al. Elevated serum levels of soluble CD163 in polymyositis and dermatomyositis: associated with macrophage infiltration in muscle tissue. J Rheumatol. 2015;42:979–87.CrossRefPubMed Peng QL, Zhang YL, Shu XM, Yang HB, Zhang L, Chen F, et al. Elevated serum levels of soluble CD163 in polymyositis and dermatomyositis: associated with macrophage infiltration in muscle tissue. J Rheumatol. 2015;42:979–87.CrossRefPubMed
15.
go back to reference Dalakas MC. Mechanisms of disease: signaling pathways and immunobiology of inflammatory myopathies. Nat Clin Pract Rheumatol. 2006;2:219–27.CrossRefPubMed Dalakas MC. Mechanisms of disease: signaling pathways and immunobiology of inflammatory myopathies. Nat Clin Pract Rheumatol. 2006;2:219–27.CrossRefPubMed
16.
go back to reference Khalil N, Bereznay O, Sporn M, Greenberg AH. Macrophage production of transforming growth factor beta and fibroblast collagen synthesis in chronic pulmonary inflammation. J Exp Med. 1989;170:727–37.CrossRefPubMed Khalil N, Bereznay O, Sporn M, Greenberg AH. Macrophage production of transforming growth factor beta and fibroblast collagen synthesis in chronic pulmonary inflammation. J Exp Med. 1989;170:727–37.CrossRefPubMed
17.
go back to reference Gibbons MA, MacKinnon AC, Ramachandran P, Dhaliwal K, Duffin R, Phythian-Adams AT, et al. Ly6Chi monocytes direct alternatively activated profibrotic macrophage regulation of lung fibrosis. Am J Respir Crit Care Med. 2011;184:569–81.CrossRefPubMed Gibbons MA, MacKinnon AC, Ramachandran P, Dhaliwal K, Duffin R, Phythian-Adams AT, et al. Ly6Chi monocytes direct alternatively activated profibrotic macrophage regulation of lung fibrosis. Am J Respir Crit Care Med. 2011;184:569–81.CrossRefPubMed
18.
go back to reference Møller HJ, Moestrup SK, Weis N, Wejse C, Nielsen H, Pedersen SS, et al. Macrophage serum markers in pneumococcal bacteremia: prediction of survival by soluble CD163. Crit Care Med. 2006;34:2561–6.CrossRefPubMed Møller HJ, Moestrup SK, Weis N, Wejse C, Nielsen H, Pedersen SS, et al. Macrophage serum markers in pneumococcal bacteremia: prediction of survival by soluble CD163. Crit Care Med. 2006;34:2561–6.CrossRefPubMed
19.
go back to reference Suzuki Y, Enomoto Y, Yokomura K, Hozumi H, Kono M, Karayama M, et al. Soluble hemoglobin scavenger receptor CD163 (sCD163) predicts mortality of community-acquired pneumonia. J Infect. 2016;73:375–7.CrossRefPubMed Suzuki Y, Enomoto Y, Yokomura K, Hozumi H, Kono M, Karayama M, et al. Soluble hemoglobin scavenger receptor CD163 (sCD163) predicts mortality of community-acquired pneumonia. J Infect. 2016;73:375–7.CrossRefPubMed
20.
go back to reference Kusi KA, Gyan BA, Goka BQ, Dodoo D, Obeng-Adjei G, Troye-Blomberg M, et al. Levels of soluble CD163 and severity of malaria in children in Ghana. Clin Vaccine Immunol. 2008;15:1456–60.CrossRefPubMedPubMedCentral Kusi KA, Gyan BA, Goka BQ, Dodoo D, Obeng-Adjei G, Troye-Blomberg M, et al. Levels of soluble CD163 and severity of malaria in children in Ghana. Clin Vaccine Immunol. 2008;15:1456–60.CrossRefPubMedPubMedCentral
21.
go back to reference Greisen SR, Moller HJ, Stengaard-Pedersen K, Hetland ML, Hørslev-Petersen K, Jørgensen A, et al. Soluble macrophage-derived CD163 is a marker of disease activity and progression in early rheumatoid arthritis. Clin Exp Rheumatol. 2011;29:689–92.PubMed Greisen SR, Moller HJ, Stengaard-Pedersen K, Hetland ML, Hørslev-Petersen K, Jørgensen A, et al. Soluble macrophage-derived CD163 is a marker of disease activity and progression in early rheumatoid arthritis. Clin Exp Rheumatol. 2011;29:689–92.PubMed
22.
go back to reference Nakayama W, Jinnin M, Makino K, Kajihara I, Makino T, Fukushima S, et al. Serum levels of soluble CD163 in patients with systemic sclerosis. Rheumatol Int. 2012;32:403–7.CrossRefPubMed Nakayama W, Jinnin M, Makino K, Kajihara I, Makino T, Fukushima S, et al. Serum levels of soluble CD163 in patients with systemic sclerosis. Rheumatol Int. 2012;32:403–7.CrossRefPubMed
23.
go back to reference Suzuki Y, Shirai M, Asada K, Miwa S, Karayama M, Nakamura Y, et al. Utility of macrophage activated marker, CD163, for diagnosis and prognosis in pulmonary tuberculosis. Ann Am Thorac Soc. 2017;14(1):57–64.PubMed Suzuki Y, Shirai M, Asada K, Miwa S, Karayama M, Nakamura Y, et al. Utility of macrophage activated marker, CD163, for diagnosis and prognosis in pulmonary tuberculosis. Ann Am Thorac Soc. 2017;14(1):57–64.PubMed
24.
go back to reference Euwer RL, Sontheimer RD. Amyopathic dermatomyositis: a review. J Invest Dermatol. 1993;100:124S–7S.CrossRefPubMed Euwer RL, Sontheimer RD. Amyopathic dermatomyositis: a review. J Invest Dermatol. 1993;100:124S–7S.CrossRefPubMed
25.
go back to reference Goh NS, Desai SR, Veeraraghavan S, Hansell DM, Copley SJ, Maher TM, et al. Interstitial lung disease in systemic sclerosis: a simple staging system. Am J Respir Crit Care Med. 2008;177:1248–54.CrossRefPubMed Goh NS, Desai SR, Veeraraghavan S, Hansell DM, Copley SJ, Maher TM, et al. Interstitial lung disease in systemic sclerosis: a simple staging system. Am J Respir Crit Care Med. 2008;177:1248–54.CrossRefPubMed
26.
go back to reference Heagerty PJ, Zheng Y. Survival model predictive accuracy and ROC curves. Biometrics. 2005;61:92–105.CrossRefPubMed Heagerty PJ, Zheng Y. Survival model predictive accuracy and ROC curves. Biometrics. 2005;61:92–105.CrossRefPubMed
27.
go back to reference Gono T, Sato S, Kawaguchi Y, Kuwana M, Hanaoka M, Katsumata Y, et al. Anti-MDA5 antibody, ferritin and IL-18 are useful for the evaluation of response to treatment in interstitial lung disease with anti-MDA5 antibody-positive dermatomyositis. Rheumatology (Oxford). 2012;51:1563–70.CrossRef Gono T, Sato S, Kawaguchi Y, Kuwana M, Hanaoka M, Katsumata Y, et al. Anti-MDA5 antibody, ferritin and IL-18 are useful for the evaluation of response to treatment in interstitial lung disease with anti-MDA5 antibody-positive dermatomyositis. Rheumatology (Oxford). 2012;51:1563–70.CrossRef
28.
go back to reference Zou J, Guo Q, Chi J, Wu H, Bao C. HRCT score and serum ferritin level are factors associated to the 1-year mortality of acute interstitial lung disease in clinically amyopathic dermatomyositis patients. Clin Rheumatol. 2015;34:707–14.CrossRefPubMed Zou J, Guo Q, Chi J, Wu H, Bao C. HRCT score and serum ferritin level are factors associated to the 1-year mortality of acute interstitial lung disease in clinically amyopathic dermatomyositis patients. Clin Rheumatol. 2015;34:707–14.CrossRefPubMed
29.
go back to reference Isoda K, Takeuchi T, Kotani T, Hata K, Shoda T, Ishida T, et al. Pre-treatment ferritin level and alveolar-arterial oxygen gradient can predict mortality rate due to acute/subacute interstitial pneumonia in dermatomyositis treated by cyclosporine a/glucocorticosteroid combination therapy: a case control study [corrected]. PLoS One. 2014;9:e89610.CrossRefPubMedPubMedCentral Isoda K, Takeuchi T, Kotani T, Hata K, Shoda T, Ishida T, et al. Pre-treatment ferritin level and alveolar-arterial oxygen gradient can predict mortality rate due to acute/subacute interstitial pneumonia in dermatomyositis treated by cyclosporine a/glucocorticosteroid combination therapy: a case control study [corrected]. PLoS One. 2014;9:e89610.CrossRefPubMedPubMedCentral
30.
go back to reference Bonner JC. Regulation of PDGF and its receptors in fibrotic diseases. Cytokine Growth Factor Rev. 2004;15:255–73.CrossRefPubMed Bonner JC. Regulation of PDGF and its receptors in fibrotic diseases. Cytokine Growth Factor Rev. 2004;15:255–73.CrossRefPubMed
31.
go back to reference Henke C, Marineili W, Jessurun J, Fox J, Harms D, Peterson M, et al. Macrophage production of basic fibroblast growth factor in the fibroproliferative disorder of alveolar fibrosis after lung injury. Am J Pathol. 1993;143:1189–99.PubMedPubMedCentral Henke C, Marineili W, Jessurun J, Fox J, Harms D, Peterson M, et al. Macrophage production of basic fibroblast growth factor in the fibroproliferative disorder of alveolar fibrosis after lung injury. Am J Pathol. 1993;143:1189–99.PubMedPubMedCentral
Metadata
Title
Clinical significance of soluble CD163 in polymyositis-related or dermatomyositis-related interstitial lung disease
Authors
Yasunori Enomoto
Yuzo Suzuki
Hironao Hozumi
Kazutaka Mori
Masato Kono
Masato Karayama
Kazuki Furuhashi
Tomoyuki Fujisawa
Noriyuki Enomoto
Yutaro Nakamura
Naoki Inui
Daisuke Suzuki
Noriyoshi Ogawa
Ran Nakashima
Tsuneyo Mimori
Toshihide Iwashita
Takafumi Suda
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 1/2017
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/s13075-016-1214-8

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