Chemokine profiles of interstitial pneumonia in patients with dermatomyositis: a case control study

Katsuhiro Oda, Takuya Kotani, Tohru Takeuchi, Takaaki Ishida, Takeshi Shoda, Kentaro Isoda, Shuzo Yoshida, Yasuichiro Nishimura, Shigeki Makino, Katsuhiro Oda, Takuya Kotani, Tohru Takeuchi, Takaaki Ishida, Takeshi Shoda, Kentaro Isoda, Shuzo Yoshida, Yasuichiro Nishimura, Shigeki Makino

Abstract

Chemokines play an important role in the pathophysiology of dermatomyositis (DM) with interstitial pneumonia (IP). However, the relation between chemokines and the disease activity or prognosis of DM-IP has not been elucidated. We evaluated the serum C-C motif chemokine ligand (CCL) 2, Th1 chemokines (C-X-C motif chemokine ligand [CXCL] 9, CXCL10, CXCL11), and Th2 chemokine (CCL17) profiles of 30 patients, and examined the relation between these chemokines and the disease activity or prognosis of DM-IP. Initial serum CCL2 level was higher in the death group (P = 0.007). To determine the cut-off points effective as poor prognostic factors of DM-IP, ROC curve analysis was carried out on initial serum CCL2 level. The value that maximized the area under the ROC curve was 894 pg/mL (sensitivity: 100%, specificity: 70.8%). Serum CCL2, CXCL9, CXCL10, and CXCL11 levels were lower at 2 weeks after treatment initiation than before treatment. Serum CCL2, CXCL10, and CXCL11 levels at 2 weeks after treatment initiation were higher in the death group. Serum levels of chemokines such as CCL2, CXCL10, and CXCL11 may be possible biomarkers of disease activity and prognosis in DM-IP, and serum CCL2 level may be useful when deciding initial treatment.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
Survival curve of patients based on their initial serum CCL2 levels, P/F ratio, KL-6, and ferritin. (A) Survival curve of patients based on their initial serum CCL2 levels (solid line: <900 pg/mL; dashed line: ≥900 pg/mL). (B) Survival curve of patients based on their initial P/F ratio (solid line: >320 torr; dashed line: ≤320 torr). (C) Survival curve of patients based on their initial KL-6 (solid line: <850 mmHg; dashed line: ≥850 mmHg). (D) Survival curve of patients based on their initial ferritin (solid line: <1600 ng/mL; dashed line: ≥1600 ng/mL). (E) Survival curve of patients based on their initial risk factors (solid line: 0 risk factors; dashed line: others). (F) Survival curve of patients based on their initial risk factors (solid line: 0 or 1 risk factor; dashed line: 2 or 3 risk factors). (G) Survival curve of patients based on their initial risk factors (solid line: others; dashed line: 3 risk factors). CCL: C-C motif chemokine ligand; P/F: PaO2/FiO2. Survival rates were calculated by the Kaplan-Meier method and compared by log-rank test. *P < 0.05.
Figure 2
Figure 2
Changes in and Comparison of serum chemokine levels of DM-IP initially and at 2 weeks after treatment between survivors and non-survivors. (A) The time series of each chemokine; (B) The comparison of serum chemokine levels initially and at 2 weeks after treatment between the survival group and the death group; CCL: C-C motif chemokine ligand; CXCL: C-X-C motif chemokine ligand; closed square: alive patients (Alive); open square: patients dead due to interstitial pneumonia (Dead). The P value was estimated by Wilcoxon’s rank sum test. *P < 0.05.
Figure 3
Figure 3
Comparison of each of the chemokine levels between anti-MDA5 antibody-positive and -negative cases. CCL: C-C motif chemokine ligand; CXCL: C-X-C motif chemokine ligand; negative: anti-MDA5 antibody-negative patients; positive: anti-MDA5 antibody-positive patients. The P value was estimated by the Mann-Whitney U-test. *P < 0.05.

References

    1. Bohan A, Peter JB. Polymyositis and dermatomyositis (first of two parts) N Engl J Med. 1975;292:344–347. doi: 10.1056/NEJM197502132920706.
    1. Bohan A, Peter JB. Polymyositis and dermatomyositis (second of two parts) N Engl J Med. 1975;292:403–407. doi: 10.1056/NEJM197502202920807.
    1. Sontheimer RD. Dermatomyositis: an overview of recent progress with emphasis on dermatologic aspects. Dermatol Clin. 2002;20:387–408. doi: 10.1016/S0733-8635(02)00021-9.
    1. Gerami P, Schope JM, McDonald L, Walling HW, Sontheimer RD. A systematic review of adult-onset clinically amyopathic dermatomyositis (dermatomyositis siné myositis): a missing link within the spectrum of the idiopathic inflammatory myopathies. J Am Acad Dermatol. 2006;54:597–613. doi: 10.1016/j.jaad.2005.10.041.
    1. Maugars YM, et al. Long-term prognosis of 69 patients with dermatomyositis or polymyositis. Clin Exp Rheumatol. 1996;14:263–274.
    1. Benbassat J, et al. Prognostic factors in polymyositis/dermatomyositis. A computer-assisted analysis of ninety-two cases. Arthritis Rheum. 1985;28:249–255. doi: 10.1002/art.1780280303.
    1. Nagasaka K, et al. Efficacy of combination treatment with cyclosporine A and corticosteroids for acute interstitial pneumonitis associated with dermatomyositis. Mod Rheumatol. 2003;13:231–238. doi: 10.3109/s10165-003-0205-1.
    1. Kotani T, et al. Combination with corticosteroids and cyclosporine-A improves pulmonary function test results and chest HRCT findings in dermatomyositis patients with acute/subacute interstitial pneumonia. Clin Rheumatol. 2011;30:1021–1028. doi: 10.1007/s10067-011-1713-6.
    1. Miyake S, et al. Usefulness of cyclosporine A on rapidly progressive interstitial pneumonia in dermatomyositis. Sarcoidosis Vasc Diffuse Lung Dis. 2002;12:128–133.
    1. Ando M, et al. Successful treatment with tacrolimus of progressive interstitial pneumonia associated with amyopathic dermatomyositis refractory to cyclosporine. Clin Rheumatol. 2010;29:443–445. doi: 10.1007/s10067-009-1358-x.
    1. Yamasaki Y, et al. Intravenous cyclophosphamide therapy for progressive interstitial pneumonia in patients with polymyositis/dermatomyositis. Rheumatology (Oxford). 2007;46:124–130. doi: 10.1093/rheumatology/kel112.
    1. Schnabel A, Hellmich B, Gross WL. Interstitial lung disease in polymyositis and dermatomyositis. Curr Rheumatol Rep. 2005;7:99–105. doi: 10.1007/s11926-005-0061-4.
    1. Kameda H, et al. Combination therapy with corticosteroids, cyclosporine A, and intravenous pulse cyclophosphamide for acute/subacute interstitial pneumonia in patients with dermatomyositis. J Rheumatol. 2005;32:1719–1726.
    1. Hoaumi H, et al. Comprehensive assessment of myositis-specific autoantibodies in polymyositis/dermatomyositis-associated interstitial lung disease. Respir Med. 2016;21:91–99.
    1. Koreeda Y, et al. Clinical and Pathological Findings of Interstitial Lung Disease Patients with Anti-Aminoacyl-tRNA Synthetase Autoantibodies. Inter Med. 2010;49:361–369. doi: 10.2169/internalmedicine.49.2889.
    1. Sato S, et al. Autoantibodies to a 140-kd polypeptide, CADM-140, in Japanese patients with clinically amyopathic dermatomyositis. Arthritis Rheum. 2005;52:1571–1576. doi: 10.1002/art.21023.
    1. Gono T, et al. Clinical manifestation and prognostic factor in anti-melanoma differentiation-associated gene 5 antibody-associated interstitial lung disease as a complication of dermatomyositis. Rheumatology (Oxford). 2010;49:1713–1719. doi: 10.1093/rheumatology/keq149.
    1. Gono T, et al. Increased ferritin predicts development and severity of acute interstitial lung disease as a complication of dermatomyositis. Rheumatology (Oxford). 2010;49:1354–1360. doi: 10.1093/rheumatology/keq073.
    1. Gono T, et al. Serum ferritin correlates with activity of anti-MDA5 antibody-associated acute interstitial lung disease as a complication of dermatomyositis. Mod Rheumatol. 2011;21:223–227. doi: 10.3109/s10165-010-0371-x.
    1. Gono T, 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;51:1563–1570. doi: 10.1093/rheumatology/kes102.
    1. Isoda K, 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. doi: 10.1371/journal.pone.0089610.
    1. Kang EH, et al. Interstitial lung disease in patients with polymyositis, dermatomyositis and amyopathic dermatomyositis. Rheumatology (Oxford). 2005;44:1282–1286. doi: 10.1093/rheumatology/keh723.
    1. Shimojima Y, et al. Coadministration of cyclosporin a with prednisolone in acute interstitial pneumonia complicating polymyositis/dermatomyositis. Clin Med Insights Arthritis Musculoskelet Disord. 2012;5:43–52.
    1. Kotani T, et al. Initial limited three-level thin-section computed tomography scorings predict the prognosis of acute/subacute interstitial pneumonia in patients with dermatomyositis. Mod Rheumatol. 2016;26:738–743. doi: 10.3109/14397595.2015.1134392.
    1. Arai S, et al. Marked increase in serum KL-6 and surfactant protein D levels during the first 4 weeks after treatment predicts poor prognosis in patients with active interstitial pneumonia associated with polymyositis/dermatomyositis. Mod Rheumatol. 2013;23:872–883. doi: 10.3109/s10165-012-0756-0.
    1. Sun WC, Sun YC, Lin H, Yan B, Shi GX. Dysregulation of the type I interferon system in adult-onset clinically amyopathic dermatomyositis has a potential contribution to the development of interstitial lung disease. Br J Dermatol. 2012;167:1236–1244. doi: 10.1111/j.1365-2133.2012.11145.x.
    1. Horai Y, et al. Serum interferon-α is a useful biomarker in patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis. Mod Rheumatol. 2015;25:85–89. doi: 10.3109/14397595.2014.900843.
    1. Gono T, et al. Cytokine profiles in polymyositis and dermatomyositis complicated by rapidly progressive or chronic interstitial lung disease. Rheumatology (Oxford). 2014;53:2196–2203. doi: 10.1093/rheumatology/keu258.
    1. Nara M, et al. Serum interleukin 6 levels as a useful prognostic predictor of clinically amyopathic dermatomyositis with rapidly progressive interstitial lung disease. Mod Rheumatol. 2014;24:633–636. doi: 10.3109/14397595.2013.844390.
    1. 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, 815245 (2014).
    1. Gono T, et al. Interleukin-18 is a key mediator in dermatomyositis: potential contribution to development of interstitial lung disease. Rheumatology (Oxford). 2010;49:1878–1881. doi: 10.1093/rheumatology/keq196.
    1. Muro Y, Sugiura K, Akiyama M. Limitations of a single-point evaluation of anti-MDA5 antibody, ferritin, and IL-18 in predicting the prognosis of interstitial lung disease with anti-MDA5 antibody-positive dermatomyositis. Clin Rheumatol. 2013;32:395–398. doi: 10.1007/s10067-012-2142-x.
    1. Chen, F., Shu, X. M., Wang, D. X., Wang, G. C. & Lu, X. Measurement and clinical significance of serum monocyte chemoattractant protein-1 in patients with polymyosits/dermatomyosits. Beijing Da Xue Bao. 44, 204–208 (2012).
    1. Kawashima T, et al. Serum TARC/CCL17 levels are increased in dermatomyositis associated with interstitial lung disease. J Dermatol Sci. 2010;60:52–54. doi: 10.1016/j.jdermsci.2010.07.012.
    1. 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;161:646–664. doi: 10.1164/ajrccm.161.2.ats3-00.
    1. Chen F, Wang D, Shu X, Nakashima R, Wang G. Anti-MDA5 antibody is associated with A/SIP and decreased T cells in peripheral blood and predicts poor prognosis of ILD in Chinese patients with dermatomyositis. Rheumatol Int. 2012;32:3909–3915. doi: 10.1007/s00296-011-2323-y.
    1. American Thoracic Society Standardization of spirometry-1987 up date. American Review of Respiratory Disease. 1987;136:1285–1298. doi: 10.1164/ajrccm/136.5.1285.
    1. American Thoracic Society Single breath carbon monoxide diffusing capacity (transfer factor). Recommendations for a standard technique. Statement of the American Thoracic Society. American Review of Respiratory Disease. 1987;136:1299–1307. doi: 10.1164/ajrccm/136.5.1299.
    1. American Thoracic Society Lung function testing: selection of reference values and interpretative strategies. American Review of Respiratory Disease. 1991;144:1202–1218. doi: 10.1164/ajrccm/144.5.1202.
    1. Kazerooni EA, et al. Thin-section CT obtained at 10-mm increments versus limited three-level thin-section CT for idiopathic pulmonary fibrosis: correlation with pathologic scoring. AJR Am J Roentgenol. 1997;169:977–983. doi: 10.2214/ajr.169.4.9308447.
    1. Gono T, et al. Hyperferritinaemia and macrophage activation in a patient with interstitial lung disease with clinically amyopathic DM. Rheumatology (Oxford). 2012;51:1336–1338. doi: 10.1093/rheumatology/kes012.
    1. Kumánovics G, Magyarlaki T, Komócsi A, Szekeres G, Czirják L. Simultaneous presence of neutrophil alveolitis and Ki-67 positivity of alveolar macrophages in dermato-/polymyositis and systemic sclerosis. Rheumatol Int. 2003;23:6–10.
    1. Kurasawa K, et al. Activation of pulmonary T cells in corticosteroid-resistant and -sensitive interstitial pneumonitis in dermatomyositis/polymyositis. Clin Exp Immunol. 2002;129:541–548. doi: 10.1046/j.1365-2249.2002.01933.x.
    1. Kameda H, Takeuchi T. Recent advances in the treatment of interstitial lung disease in patients with polymyositis/dermatomyositis. Endocr Metab Immune Disord Drug Targets. 2006;6:409–415. doi: 10.2174/187153006779025775.
    1. Enelow RI, et al. Structural and functional consequences of alveolar cell recognition by CD8(+) T lymphocytes in experimental lung disease. J Clin Invest. 1998;102:1653–1661. doi: 10.1172/JCI4174.
    1. Richards TJ, et al. Characterization and peripheral blood biomarker assessment of Jo-1 antibody-positive interstitial lung disease. Arthritis Rheum. 2009;60:2183–2192. doi: 10.1002/art.24631.

Source: PubMed

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

3
Abonneren