266
Views
19
CrossRef citations to date
0
Altmetric
Review

Facts and promises on lung biomarkers in interstitial lung diseases

, &

References

  • Travis WD, Costabel U, Hansell DM, et al. An official American Thoracic Society/European Respiratory Society statement: Update of the international multidisciplinary classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med 2013;188(6):733-48
  • Raghu G, Collard HR, Egan JJ, et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med 2011;183(6):788-824
  • Olson AL, Brown KK, Fischer A. Connective tissue disease-associated lung disease. Immunol Allergy Clin North Am 2012;32(4):513-36
  • Selman M, Pardo A. Revealing the pathogenic and aging-related mechanisms of the enigmatic idiopathic pulmonary fibrosis. an integral model. Am J Respir Crit Care Med 2014;189(10):1161-72
  • Prasse A, Muller-Quernheim J. Non-invasive biomarkers in pulmonary fibrosis. Respirology 2009;14(6):788-95
  • Lota HK, Renzoni EA. Circulating biomarkers of interstitial lung disease in systemic sclerosis. Int J Rheumatol 2012;2012:121439
  • Bonella F, Costabel U. Biomarkers in connective tissue disease-associated interstitial lung disease. Semin Respir Crit Care Med 2014;35(2):181-200
  • De Lauretis A, Renzoni EA. Molecular biomarkers in interstitial lung diseases. Mol Diagn Ther 2014;18(5):505-22
  • Castelino FV, Varga J. Current status of systemic sclerosis biomarkers: applications for diagnosis, management and drug development. Expert Rev Clin Immunol 2013;9(11):1077-90
  • Ishikawa N, Hattori N, Yokoyama A, Kohno N. Utility of KL-6/MUC1 in the clinical management of interstitial lung diseases. Respir Investig 2012;50(1):3-13
  • Ohshimo S, Yokoyama A, Hattori N, et al. KL-6, a human MUC1 mucin, promotes proliferation and survival of lung fibroblasts. Biochem Biophys Res Commun 2005;338(4):1845-52
  • Song JW, Do KH, Jang SJ, et al. Blood biomarkers MMP-7 and SP-A: predictors of outcome in idiopathic pulmonary fibrosis. Chest 2013;143(5):1422-9
  • Satoh H, Kurishima K, Ishikawa H, Ohtsuka M. Increased levels of KL-6 and subsequent mortality in patients with interstitial lung diseases. J Intern Med 2006;260(5):429-34
  • Bonella F, Ohshimo S, Miaotian C, et al. Serum KL-6 is a predictor of outcome in pulmonary alveolar proteinosis. Orphanet J Rare Dis 2013;8:53
  • Bonella F, Volpe A, Caramaschi P, et al. Surfactant protein D and KL-6 serum levels in systemic sclerosis: correlation with lung and systemic involvement. Sarcoidosis Vasc Diffuse Lung Dis 2011;28(1):27-33
  • Johannson K, Collard HR. Acute exacerbation of idiopathic pulmonary fibrosis: a proposal. Curr Respir Care Rep 2013;2(4
  • Collard HR, Calfee CS, Wolters PJ, et al. Plasma biomarker profiles in acute exacerbation of idiopathic pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol 2010;299(1):L3-7
  • Yamane K, Ihn H, Kubo M, et al. Serum levels of KL-6 as a useful marker for evaluating pulmonary fibrosis in patients with systemic sclerosis. J Rheumatol 2000;27(4):930-4
  • Yanaba K, Hasegawa M, Hamaguchi Y, et al. Longitudinal analysis of serum KL-6 levels in patients with systemic sclerosis: association with the activity of pulmonary fibrosis. Clin Exp Rheumatol 2003;21(4):429-36
  • Yanaba K, Hasegawa M, Takehara K, Sato S. Comparative study of serum surfactant protein-D and KL-6 concentrations in patients with systemic sclerosis as markers for monitoring the activity of pulmonary fibrosis. J Rheumatol 2004;31(6):1112-20
  • Hant FN, Ludwicka-Bradley A, Wang HJ, et al. Surfactant protein D and KL-6 as serum biomarkers of interstitial lung disease in patients with scleroderma. J Rheumatol 2009;36(4):773-80
  • Doishita S, Inokuma S, Asashima H, et al. Serum KL-6 level as an indicator of active or inactive interstitial pneumonitis associated with connective tissue diseases. Intern Med 2011;50(23):2889-92
  • Kumanovics G, Minier T, Radics J, et al. Comprehensive investigation of novel serum markers of pulmonary fibrosis associated with systemic sclerosis and dermato/polymyositis. Clin Exp Rheumatol 2008;26(3):414-20
  • Kumanovics G, Gorbe E, Minier T, et al. Follow-up of serum KL-6 lung fibrosis biomarker levels in 173 patients with systemic sclerosis. Clin Exp Rheumatol 2014;32(6 Suppl 86):138-44
  • Janssen R, Sato H, Grutters JC, et al. Study of Clara cell 16, KL-6, and surfactant protein-D in serum as disease markers in pulmonary sarcoidosis. Chest 2003;124(6):2119-25
  • Janssen R, Kruit A, Grutters JC, et al. The mucin-1 568 adenosine to guanine polymorphism influences serum Krebs von den Lungen-6 levels. Am J Respir Cell Mol Biol 2006;34(4):496-9
  • Horimasu Y, Hattori N, Ishikawa N, et al. Different MUC1 gene polymorphisms in German and Japanese ethnicities affect serum KL-6 levels. Respir Med 2012;106(12):1756-64
  • Pastva AM, Wright JR, Williams KL. Immunomodulatory roles of surfactant proteins A and D: implications in lung disease. Proc Am Thorac Soc 2007;4(3):252-7
  • Janssen R, Grutters JC, Sato H, et al. Analysis of KL-6 and SP-D as disease markers in bird fancier’s lung. Sarcoidosis Vasc Diffuse Lung Dis 2005;22(1):51-7
  • Elhaj M, Charles J, Pedroza C, et al. Can serum surfactant protein D or CC-chemokine ligand 18 predict outcome of interstitial lung disease in patients with early systemic sclerosis? J Rheumatol 2013;40(7):1114-20
  • Ihn H, Asano Y, Kubo M, et al. Clinical significance of serum surfactant protein D (SP-D) in patients with polymyositis/dermatomyositis: correlation with interstitial lung disease. Rheumatology (Oxford) 2002;41(11):1268-72
  • Kunitake R, Kuwano K, Yoshida K, et al. KL-6, surfactant protein A and D in bronchoalveolar lavage fluid from patients with pulmonary sarcoidosis. Respiration 2001;68(5):488-95
  • Kobayashi M, Takeuchi T, Ohtsuki Y. Differences in the immunolocalization of surfactant protein (SP)-A, SP-D, and KL-6 in pulmonary alveolar proteinosis. Pathol Int 2008;58(3):203-7
  • Kinder BW, Brown KK, McCormack FX, et al. Serum surfactant protein-A is a strong predictor of early mortality in idiopathic pulmonary fibrosis. Chest 2009;135(6):1557-63
  • Takahashi H, Kuroki Y, Tanaka H, et al. Serum levels of surfactant proteins A and D are useful biomarkers for interstitial lung disease in patients with progressive systemic sclerosis. Am J Respir Crit Care Med 2000;162(1):258-63
  • Horimasu Y, Hattori N, Ishikawa N, et al. Differences in serum SP-D levels between German and Japanese subjects are associated with SFTPD gene polymorphisms. BMC Med Genet 2014;15:4
  • Bernard A, Hermans C, Van Houte G. Transient increase of serum Clara cell protein (CC16) after exposure to smoke. Occup Environ Med 1997;54(1):63-5
  • Petrek M, Hermans C, Kolek V, et al. Clara cell protein (CC16) in serum and bronchoalveolar lavage fluid of subjects exposed to asbestos. Biomarkers 2002;7(1):58-67
  • Hermans C, Petrek M, Kolek V, et al. Serum Clara cell protein (CC16), a marker of the integrity of the air-blood barrier in sarcoidosis. Eur Respir J 2001;18(3):507-14
  • Kucejko W, Chyczewska E, Naumnik W, Ossolinska M. Concentration of surfactant protein D, Clara cell protein CC-16 and IL-10 in bronchoalveolar lavage (BAL) in patients with sarcoidosis, hypersensivity pneumonitis and idiopathic pulmonary fibrosis. Folia Histochem Cytobiol 2009;47(2):225-30
  • Hasegawa M, Fujimoto M, Hamaguchi Y, et al. Use of serum clara cell 16-kDa (CC16) levels as a potential indicator of active pulmonary fibrosis in systemic sclerosis. J Rheumatol 2011;38(5):877-84
  • Cottin V, Nunes H, Brillet PY, et al. Combined pulmonary fibrosis and emphysema: a distinct underrecognised entity. Eur Respir J 2005;26(4):586-93
  • Kokuho N, Ishii T, Kamio K, et al. Diagnostic values for club cell secretory protein (CC16) in serum of patients of combined pulmonary fibrosis and emphysema. COPD 2014. [ Epub ahead of print
  • Johansen JS. Studies on serum YKL-40 as a biomarker in diseases with inflammation, tissue remodelling, fibroses and cancer. Dan Med Bull 2006;53(2):172-209
  • Specjalski K, Chelminska M, Jassem E. YKL-40 protein correlates with the phenotype of asthma. Lung 2015;193(2):189-94
  • Specjalski K, Jassem E. YKL-40 protein is a marker of asthma. J Asthma 2011;48(8):767-72
  • Korthagen NM, van Moorsel CH, Barlo NP, et al. Serum and BALF YKL-40 levels are predictors of survival in idiopathic pulmonary fibrosis. Respir Med 2011;105(1):106-13
  • Nordenbaek C, Johansen JS, Halberg P, et al. High serum levels of YKL-40 in patients with systemic sclerosis are associated with pulmonary involvement. Scand J Rheumatol 2005;34(4):293-7
  • Stamenkovic I. Extracellular matrix remodelling: the role of matrix metalloproteinases. J Pathol 2003;200(4):448-64
  • Sand JM, Larsen L, Hogaboam C, et al. MMP mediated degradation of type IV collagen alpha 1 and alpha 3 chains reflects basement membrane remodeling in experimental and clinical fibrosis–validation of two novel biomarker assays. PLoS ONE 2013;8(12):e84934
  • Rosas IO, Richards TJ, Konishi K, et al. MMP1 and MMP7 as potential peripheral blood biomarkers in idiopathic pulmonary fibrosis. PLoS Med 2008;5(4):e93
  • Richards TJ, Kaminski N, Baribaud F, et al. Peripheral blood proteins predict mortality in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2012;185(1):67-76
  • Choi KH, Lee HB, Jeong MY, et al. The role of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in cryptogenic organizing pneumonia. Chest 2002;121(5):1478-85
  • Suga M, Iyonaga K, Okamoto T, et al. Characteristic elevation of matrix metalloproteinase activity in idiopathic interstitial pneumonias. Am J Respir Crit Care Med 2000;162(5):1949-56
  • Kim WU, Min SY, Cho ML, et al. Elevated matrix metalloproteinase-9 in patients with systemic sclerosis. Arthr Res Ther 2005;7(1):R71-9
  • Andersen GN, Nilsson K, Pourazar J, et al. Bronchoalveolar matrix metalloproteinase 9 relates to restrictive lung function impairment in systemic sclerosis. Respir Med 2007;101(10):2199-206
  • Moinzadeh P, Krieg T, Hellmich M, et al. Elevated MMP-7 levels in patients with systemic sclerosis: correlation with pulmonary involvement. Exp Dermatol 2011;20(9):770-3
  • Manetti M, Ibba-Manneschi L, Fatini C, et al. Association of a functional polymorphism in the matrix metalloproteinase-12 promoter region with systemic sclerosis in an Italian population. J Rheumatol 2010;37(9):1852-7
  • Kikuchi K, Kubo M, Sato S, et al. Serum tissue inhibitor of metalloproteinases in patients with systemic sclerosis. J Am Acad Dermatol 1995;33(6):973-8
  • Oka S, Furukawa H, Shimada K, et al. Serum biomarker analysis of collagen disease patients with acute-onset diffuse interstitial lung disease. BMC Immunol 2013;14:9
  • Taniguchi T, Asano Y, Akamata K, et al. Serum levels of ADAM12-S: possible association with the initiation and progression of dermal fibrosis and interstitial lung disease in patients with systemic sclerosis. J Eur Acad Dermatol Venereol 2013;27(6):747-53
  • Barry-Hamilton V, Spangler R, Marshall D, et al. Allosteric inhibition of lysyl oxidase-like-2 impedes the development of a pathologic microenvironment. Nat Med 2010;16(9):1009-17
  • Chien JW, Richards TJ, Gibson KF, et al. Serum lysyl oxidase-like 2 levels and idiopathic pulmonary fibrosis disease progression. Eur Respir J 2014;43(5):1430-8
  • A Phase II study to see if simtuzumab (GS-6624) is safe and works in idiopathic pulmonary fibrosis (IPF) (RAINIER). Available from: https://clinicaltrials.gov/ct2/show/NCT01769196
  • Rimar D, Rosner I, Nov Y, et al. Brief report: lysyl oxidase is a potential biomarker of fibrosis in systemic sclerosis. Arthr Rheumatol 2014;66(3):726-30
  • Prospective study of fibrosis in the lung endpoints (PROFILE - Central England). Available from: https://clinicaltrials.gov/ct2/show/NCT01134822
  • Prospective observation of fibrosis in the lung clinical endpoints study (PROFILE). Available from: https://clinicaltrials.gov/ct2/show/NCT01110694
  • Jenkins RG, Simpson JK, Saini G, et al. Longitudinal change in collagen degradation biomarkers in idiopathic pulmonary fibrosis: an analysis from the prospective, multicentre PROFILE study. Lancet Respir Med 2015;3(6):462-72.
  • Naik PK, Bozyk PD, Bentley JK, et al. Periostin promotes fibrosis and predicts progression in patients with idiopathic pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol 2012;303(12):L1046-56
  • Okamoto M, Hoshino T, Kitasato Y, et al. Periostin, a matrix protein, is a novel biomarker for idiopathic interstitial pneumonias. Eur Respir J 2011;37(5):1119-27
  • Tajiri M, Okamoto M, Fujimoto K, et al. Serum level of periostin can predict long-term outcome of idiopathic pulmonary fibrosis. Respir Investig 2015;53(2):73-81
  • Prasse A, Pechkovsky DV, Toews GB, et al. CCL18 as an indicator of pulmonary fibrotic activity in idiopathic interstitial pneumonias and systemic sclerosis. Arthritis Rheum 2007;56(5):1685-93
  • Tiev KP, Hua-Huy T, Kettaneh A, et al. Serum CC chemokine ligand-18 predicts lung disease worsening in systemic sclerosis. Eur Respir J 2011;38(6):1355-60
  • Kodera M, Hasegawa M, Komura K, et al. Serum pulmonary and activation-regulated chemokine/CCL18 levels in patients with systemic sclerosis: a sensitive indicator of active pulmonary fibrosis. Arthritis Rheum 2005;52(9):2889-96
  • Prasse A, Probst C, Bargagli E, et al. Serum CC-chemokine ligand 18 concentration predicts outcome in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2009;179(8):717-23
  • Assassi S, Sharif R, Lasky RE, et al. Predictors of interstitial lung disease in early systemic sclerosis: a prospective longitudinal study of the GENISOS cohort. Arthr Res Ther 2010;12(5):R166
  • Hasegawa M, Sato S, Takehara K. Augmented production of chemokines (monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1alpha (MIP-1alpha) and MIP-1beta) in patients with systemic sclerosis: MCP-1 and MIP-1alpha may be involved in the development of pulmonary fibrosis. Clin Exp Immunol 1999;117(1):159-65
  • Carulli MT, Handler C, Coghlan JG, et al. Can CCL2 serum levels be used in risk stratification or to monitor treatment response in systemic sclerosis? Ann Rheum Dis 2008;67(1):105-9
  • Antonelli A, Ferri C, Fallahi P, et al. CXCL10 (alpha) and CCL2 (beta) chemokines in systemic sclerosis–a longitudinal study. Rheumatology (Oxford) 2008;47(1):45-9
  • Hasegawa M, Fujimoto M, Matsushita T, et al. Serum chemokine and cytokine levels as indicators of disease activity in patients with systemic sclerosis. Clin Rheumatol 2011;30(2):231-7
  • Campioni D, Lo Monaco A, Lanza F, et al. CXCR4 pos circulating progenitor cells coexpressing monocytic and endothelial markers correlating with fibrotic clinical features are present in the peripheral blood of patients affected by systemic sclerosis. Haematologica 2008;93(8):1233-7
  • Schmidt K, Martinez-Gamboa L, Meier S, et al. Bronchoalveoloar lavage fluid cytokines and chemokines as markers and predictors for the outcome of interstitial lung disease in systemic sclerosis patients. Arthr Res Ther 2009;11(4):R111
  • Moore BB, Kolodsick JE, Thannickal VJ, et al. CCR2-mediated recruitment of fibrocytes to the alveolar space after fibrotic injury. Am J Pathol 2005;166(3):675-84
  • Garcia G, Ganesh R, Fernando JM, et al. A Phase II, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study of the safety and efficacy of CNTO 888 (Carlumab) in patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2013;187:A3376
  • Su R, Nguyen ML, Agarwal MR, et al. Interferon-inducible chemokines reflect severity and progression in sarcoidosis. Respir Res 2013;14(1):121
  • Romagnani P, Maggi L, Mazzinghi B, et al. CXCR3-mediated opposite effects of CXCL10 and CXCL4 on TH1 or TH2 cytokine production. J Allergy Clin Immunol 2005;116(6):1372-9
  • van Bon L, Affandi AJ, Broen J, et al. Proteome-wide analysis and CXCL4 as a biomarker in systemic sclerosis. N Engl J Med 2014;370(5):433-43
  • Keijsers RG, Verzijlbergen FJ, Oyen WJ, et al. 18F-FDG PET, genotype-corrected ACE and sIL-2R in newly diagnosed sarcoidosis. Eur J Nucl Med Mol Imaging 2009;36(7):1131-7
  • Vorselaars AD, van Moorsel CH, Zanen P, et al. ACE and sIL-2R correlate with lung function improvement in sarcoidosis during methotrexate therapy. Respir Med 2015;109(2):279-85
  • Homolka J, Ziegenhagen MW, Gaede KI, et al. Systemic immune cell activation in a subgroup of patients with idiopathic pulmonary fibrosis. Respiration 2003;70(3):262-9
  • Simeonova PP, Toriumi W, Kommineni C, et al. Molecular regulation of IL-6 activation by asbestos in lung epithelial cells: role of reactive oxygen species. J Immunol 1997;159(8):3921-8
  • Tripathi SS, Mishra V, Shukla M, et al. IL-6 receptor-mediated lung Th2 cytokine networking in silica-induced pulmonary fibrosis. Arch Toxicol 2010;84(12):947-55
  • Chang CH, Hsiao CF, Yeh YM, et al. Circulating interleukin-6 level is a prognostic marker for survival in advanced nonsmall cell lung cancer patients treated with chemotherapy. Int J Cancer 2013;132(9):1977-85
  • Barnes TC, Anderson ME, Moots RJ. The many faces of interleukin-6: the role of IL-6 in inflammation, vasculopathy, and fibrosis in systemic sclerosis. Int J Rheumatol 2011;2011:721608
  • De Lauretis A, Sestini P, Pantelidis P, et al. Serum Interleukin 6 Is Predictive of Early Functional Decline and Mortality in Interstitial Lung Disease Associated with Systemic Sclerosis. J Rheumatol 2013;40(4):435-46
  • Yoshimoto T, Takeda K, Tanaka T, et al. IL-12 up-regulates IL-18 receptor expression on T cells, Th1 cells, and B cells: synergism with IL-18 for IFN-gamma production. J Immunol 1998;161(7):3400-7
  • Antoniou KM, Tzouvelekis A, Alexandrakis MG, et al. Upregulation of Th1 cytokine profile (IL-12, IL-18) in bronchoalveolar lavage fluid in patients with pulmonary sarcoidosis. J Interf Cytok Res 2006;26(6):400-5
  • Mroz RM, Korniluk M, Stasiak-Barmuta A, Chyczewska E. Increased levels of interleukin-12 and interleukin-18 in bronchoalveolar lavage fluid of patients with pulmonary sarcoidosis. J Physiol Pharmacol 2008;59(Suppl 6):507-13
  • Mroz RM, Korniluk M, Stasiak-Barmuta A, Chyczewska E. Upregulation of Th1 cytokine profile in bronchoalveolar lavage fluid of patients with hypersensitivity pneumonitis. J Physiol Pharmacol 2008;59(Suppl 6):499-505
  • Liu DH, Cui W, Chen Q, Huang CM. Can circulating interleukin-18 differentiate between sarcoidosis and idiopathic pulmonary fibrosis? Scand J Clin Lab Invest 2011;71(7):593-7
  • Antoniou KM, Alexandrakis MG, Sfiridaki K, et al. Th1 cytokine pattern (IL-12 and IL-18) in bronchoalveolar lavage fluid (BALF) before and after treatment with interferon gamma-1b (IFN-gamma-1b) or colchicine in patients with idiopathic pulmonary fibrosis (IPF/UIP). Sarcoidosis Vasc Diffuse Lung Dis 2004;21(2):105-10
  • Borthwick LA, Barron L, Hart KM, et al. Macrophages are critical to the maintenance of IL-13-dependent lung inflammation and fibrosis. Mucosal Immunol 2015. [ Epub ahead of print
  • Zhu Z, Ma B, Zheng T, et al. IL-13-induced chemokine responses in the lung: role of CCR2 in the pathogenesis of IL-13-induced inflammation and remodeling. J Immunol 2002;168(6):2953-62
  • Keane MP, Gomperts BN, Weigt S, et al. IL-13 is pivotal in the fibro-obliterative process of bronchiolitis obliterans syndrome. J Immunol 2007;178(1):511-19
  • Belperio JA, Dy M, Burdick MD, et al. Interaction of IL-13 and C10 in the pathogenesis of bleomycin-induced pulmonary fibrosis. Am J Respir Cell Mol Biol 2002;27(4):419-27
  • Barnes JC, Lumsden RV, Worrell J, et al. CXCR3 is required for the IL-13 mediated upregulation of IL-13Ralpha2 in pulmonary fibroblasts. Am J Respir Cell Mol Biol 2014. [ Epub ahead of print
  • A study of lebrikizumab in patients with idiopathic pulmonary fibrosis. Available from: https://clinicaltrials.gov/ct2/show/NCT01872689
  • Efficacy and safety of SAR156597 in the treatment of idiopathic pulmonary fibrosis. Available from: https://clinicaltrials.gov/ct2/show/NCT02345070
  • Kurasawa K, Hirose K, Sano H, et al. Increased interleukin-17 production in patients with systemic sclerosis. Arthritis Rheum 2000;43(11):2455-63
  • Komura K, Fujimoto M, Hasegawa M, et al. Increased serum interleukin 23 in patients with systemic sclerosis. J Rheumatol 2008;35(1):120-5
  • Wuttge DM, Wildt M, Geborek P, et al. Serum IL-15 in patients with early systemic sclerosis: a potential novel marker of lung disease. Arthr Res Ther 2007;9(5):R85
  • Francois A, Gombault A, Villeret B, et al. B cell activating factor is central to bleomycin- and IL-17-mediated experimental pulmonary fibrosis. J Autoimmun 2015;56:1-11
  • Bargagli E, Olivieri C, Cintorino M, et al. Calgranulin B (S100A9/MRP14): a key molecule in idiopathic pulmonary fibrosis? Inflammation 2011;34(2):85-91
  • van Bon L, Cossu M, Loof A, et al. Proteomic analysis of plasma identifies the Toll-like receptor agonists S100A8/A9 as a novel possible marker for systemic sclerosis phenotype. Ann Rheum Dis 2014;73(8):1585-9
  • Sharma P, Smith I, Maguire G, et al. Clinical value of ACE genotyping in diagnosis of sarcoidosis. Lancet 1997;349(9065):1602-3
  • Kruit A, Grutters JC, Gerritsen WB, et al. ACE I/D-corrected Z-scores to identify normal and elevated ACE activity in sarcoidosis. Respir Med 2007;101(3):510-15
  • Cho SJ, Weiden MD, Lee CG. Chitotriosidase in the Pathogenesis of Inflammation, Interstitial Lung Diseases and COPD. Allergy Asthma Immunol Res 2015;7(1):14-21
  • Bargagli E, Bennett D, Maggiorelli C, et al. Human chitotriosidase: a sensitive biomarker of sarcoidosis. J Clin Immunol 2013;33(1):264-70
  • Gunther A, Korfei M, Mahavadi P, et al. Unravelling the progressive pathophysiology of idiopathic pulmonary fibrosis. Eur Respir Rev 2012;21(124):152-60
  • Uguccioni M, Pulsatelli L, Grigolo B, et al. Endothelin-1 in idiopathic pulmonary fibrosis. J Clin Pathol 1995;48(4):330-4
  • Reichenberger F, Schauer J, Kellner K, et al. Different expression of endothelin in the bronchoalveolar lavage in patients with pulmonary diseases. Lung 2001;179(3):163-74
  • Cambrey AD, Harrison NK, Dawes KE, et al. Increased levels of endothelin-1 in bronchoalveolar lavage fluid from patients with systemic sclerosis contribute to fibroblast mitogenic activity in vitro. Am J Respir Cell Mol Biol 1994;11(4):439-45
  • Abraham DJ, Vancheeswaran R, Dashwood MR, et al. Increased levels of endothelin-1 and differential endothelin type A and B receptor expression in scleroderma-associated fibrotic lung disease. Am J Pathol 1997;151(3):831-41
  • Vancheeswaran R, Magoulas T, Efrat G, et al. Circulating endothelin-1 levels in systemic sclerosis subsets–a marker of fibrosis or vascular dysfunction? J Rheumatol 1994;21(10):1838-44
  • Ihn H, Sato S, Fujimoto M, et al. Increased serum levels of soluble vascular cell adhesion molecule-1 and E-selectin in patients with systemic sclerosis. Br J Rheumatol 1998;37(11):1188-92
  • Kuryliszyn-Moskal A, Klimiuk PA, Sierakowski S. Soluble adhesion molecules (sVCAM-1, sE-selectin), vascular endothelial growth factor (VEGF) and endothelin-1 in patients with systemic sclerosis: relationship to organ systemic involvement. Clin Rheumatol 2005;24(2):111-16
  • Bellini A, Mattoli S. The role of the fibrocyte, a bone marrow-derived mesenchymal progenitor, in reactive and reparative fibroses. Laborat Investig 2007;87(9):858-70
  • Mattoli S, Bellini A, Schmidt M. The role of a human hematopoietic mesenchymal progenitor in wound healing and fibrotic diseases and implications for therapy. Curr Stem Cell Res Ther 2009;4(4):266-80
  • Moeller A, Gilpin SE, Ask K, et al. Circulating fibrocytes are an indicator of poor prognosis in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2009;179(7):588-94
  • Borie R, Quesnel C, Phin S, et al. Detection of alveolar fibrocytes in idiopathic pulmonary fibrosis and systemic sclerosis. PLoS One 2013;8(1):e53736
  • Kotsianidis I, Nakou E, Bouchliou I, et al. Global impairment of CD4+CD25+FOXP3+ regulatory T cells in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2009;179(12):1121-30
  • Suzuki K, Okuno T, Yamamoto M, et al. Semaphorin 7A initiates T-cell-mediated inflammatory responses through alpha1beta1 integrin. Nature 2007;446(7136):680-4
  • Reilkoff RA, Peng H, Murray LA, et al. Semaphorin 7a+ regulatory T cells are associated with progressive idiopathic pulmonary fibrosis and are implicated in transforming growth factor-beta1-induced pulmonary fibrosis. Am J Respir Crit Care Med 2013;187(2):180-8
  • Borie R, Kannengiesser C, Nathan N, et al. Familial pulmonary fibrosis. Rev Mal Respir 2015;32(4):413-34
  • Mathai SK, Schwartz DA, Warg LA. Genetic susceptibility and pulmonary fibrosis. Curr Opin Pulm Med 2014;20(5):429-35
  • Spagnolo P, Grunewald J, du Bois RM. Genetic determinants of pulmonary fibrosis: evolving concepts. Lancet Respir Med 2014;2(5):416-28
  • Javaheri S, Lederer DH, Pella JA, et al. Idiopathic pulmonary fibrosis in monozygotic twins. The importance of genetic predisposition. Chest 1980;78(4):591-4
  • Bonanni PP, Frymoyer JW, Jacox RF. A family study of idiopathic pulmonary fibrosis. A possible dysproteinemic and genetically determined disease. Am J Med 1965;39:411-21
  • Solliday NH, Williams JA, Gaensler EA, et al. Familial chronic interstitial pneumonia. Am Rev Respir Dis 1973;108(2):193-204
  • Bitterman PB, Rennard SI, Keogh BA, et al. Familial idiopathic pulmonary fibrosis. Evidence of lung inflammation in unaffected family members. N Engl J Med 1986;314(21):1343-7
  • Tsukahara M, Kajii T. Interstitial pulmonary fibrosis in two sisters. Possible autosomal recessive inheritance. Jpn J Hum Genet 1983;28(4):263-7
  • Campo I, Zorzetto M, Mariani F, et al. A large kindred of pulmonary fibrosis associated with a novel ABCA3 gene variant. Respir Res 2014;15:43
  • Lawson WE, Loyd JE, Degryse AL. Genetics in pulmonary fibrosis–familial cases provide clues to the pathogenesis of idiopathic pulmonary fibrosis. Am J Med Sci 2011;341(6):439-43
  • Fingerlin TE, Murphy E, Zhang W, et al. Genome-wide association study identifies multiple susceptibility loci for pulmonary fibrosis. Nat Genet 2013;45(6):613-20.
  • Lee HL, Ryu JH, Wittmer MH, et al. Familial idiopathic pulmonary fibrosis: clinical features and outcome. Chest 2005;127(6):2034-41
  • Lee HY, Seo JB, Steele MP, et al. High-resolution CT scan findings in familial interstitial pneumonia do not conform to those of idiopathic interstitial pneumonia. Chest 2012;142(6):1577-83
  • Steele MP, Speer MC, Loyd JE, et al. Clinical and pathologic features of familial interstitial pneumonia. Am J Respir Crit Care Med 2005;172(9):1146-52
  • Seibold MA, Wise AL, Speer MC, et al. A common MUC5B promoter polymorphism and pulmonary fibrosis. N Engl J Med 2011;364(16):1503-12
  • Peljto AL, Zhang Y, Fingerlin TE, et al. Association between the MUC5B promoter polymorphism and survival in patients with idiopathic pulmonary fibrosis. JAMA 2013;309(21):2232-9
  • Stock CJ, Sato H, Fonseca C, et al. Mucin 5B promoter polymorphism is associated with idiopathic pulmonary fibrosis but not with development of lung fibrosis in systemic sclerosis or sarcoidosis. Thorax 2013;68(5):436-41
  • Hunninghake GM, Hatabu H, Okajima Y, et al. MUC5B promoter polymorphism and interstitial lung abnormalities. N Engl J Med 2013;368(23):2192-200
  • Plantier L, Crestani B, Wert SE, et al. Ectopic respiratory epithelial cell differentiation in bronchiolised distal airspaces in idiopathic pulmonary fibrosis. Thorax 2011;66(8):651-7
  • Noth I, Zhang Y, Ma SF, et al. Genetic variants associated with idiopathic pulmonary fibrosis susceptibility and mortality: a genome-wide association study. Lancet Respir Med 2013;1(4):309-17
  • Calado RT. Telomeres in lung diseases. Prog Mol Biol Transl Sci 2014;125:173-83
  • Diaz de Leon A, Cronkhite JT, Katzenstein AL, et al. Telomere lengths, pulmonary fibrosis and telomerase (TERT) mutations. PLoS One 2010;5(5):e10680
  • Cronkhite JT, Xing C, Raghu G, et al. Telomere shortening in familial and sporadic pulmonary fibrosis. Am J Respir Crit Care Med 2008;178(7):729-37
  • Kropski JA, Mitchell DB, Markin C, et al. A novel dyskerin (DKC1) mutation is associated with familial interstitial pneumonia. Chest 2014;146(1):e1-7
  • Stuart BD, Lee JS, Kozlitina J, et al. Effect of telomere length on survival in patients with idiopathic pulmonary fibrosis: an observational cohort study with independent validation. Lancet Respir Med 2014;2(7):557-65
  • Tanjore H, Blackwell TS, Lawson WE. Emerging evidence for endoplasmic reticulum stress in the pathogenesis of idiopathic pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol 2012;302(8):L721-9
  • Nogee LM, Dunbar AEIII, Wert SE, et al. A mutation in the surfactant protein C gene associated with familial interstitial lung disease. N Engl J Med 2001;344(8):573-9
  • Thomas AQ, Lane K, Phillips JIII, et al. Heterozygosity for a surfactant protein C gene mutation associated with usual interstitial pneumonitis and cellular nonspecific interstitial pneumonitis in one kindred. Am J Respir Crit Care Med 2002;165(9):1322-8
  • Brasch F, Griese M, Tredano M, et al. Interstitial lung disease in a baby with a de novo mutation in the SFTPC gene. Eur Respir J 2004;24(1):30-9
  • Wang Y, Kuan PJ, Xing C, et al. Genetic defects in surfactant protein A2 are associated with pulmonary fibrosis and lung cancer. Am J Hum Genet 2009;84(1):52-9
  • Whitsett JA, Wert SE, Weaver TE. Alveolar surfactant homeostasis and the pathogenesis of pulmonary disease. Annu Rev Med 2010;61:105-19
  • Young LR, Nogee LM, Barnett B, et al. Usual interstitial pneumonia in an adolescent with ABCA3 mutations. Chest 2008;134(1):192-5
  • Papiris SA, Tsirigotis P, Kolilekas L, et al. Pulmonary alveolar proteinosis: time to shift? Expert Rev Respir Med 2015;9(3):1-13
  • Hsu AP, Sampaio EP, Khan J, et al. Mutations in GATA2 are associated with the autosomal dominant and sporadic monocytopenia and mycobacterial infection (MonoMAC) syndrome. Blood 2011;118(10):2653-5
  • Suzuki T, Sakagami T, Young LR, et al. Hereditary pulmonary alveolar proteinosis: pathogenesis, presentation, diagnosis, and therapy. Am J Respir Crit Care Med 2010;182(10):1292-304
  • Suzuki T, Maranda B, Sakagami T, et al. Hereditary pulmonary alveolar proteinosis caused by recessive CSF2RB mutations. Eur Respir J 2011;37(1):201-4
  • Hodgson U, Pulkkinen V, Dixon M, et al. ELMOD2 is a candidate gene for familial idiopathic pulmonary fibrosis. Am J Hum Genet 2006;79(1):149-54
  • Fischer A, Grunewald J, Spagnolo P, et al. Genetics of sarcoidosis. Semin Respir Crit Care Med 2014;35(3):296-306
  • Spagnolo P, Grunewald J. Recent advances in the genetics of sarcoidosis. J Med Genet 2013;50(5):290-7
  • Odani T, Yasuda S, Ota Y, et al. Up-regulated expression of HLA-DRB5 transcripts and high frequency of the HLA-DRB5*01:05 allele in scleroderma patients with interstitial lung disease. Rheumatology (Oxford) 2012;51(10):1765-74
  • Goldberg AD, Allis CD, Bernstein E. Epigenetics: a landscape takes shape. Cell 2007;128(4):635-8
  • Fraga MF, Ballestar E, Paz MF, et al. Epigenetic differences arise during the lifetime of monozygotic twins. Proc Natl Acad Sci USA 2005;102(30):10604-9
  • Bjornsson HT, Sigurdsson MI, Fallin MD, et al. Intra-individual change over time in DNA methylation with familial clustering. JAMA 2008;299(24):2877-83
  • Yang IV, Schwartz DA. Epigenetic control of gene expression in the lung. Am J Respir Crit Care Med 2011;183(10):1295-301
  • Portela A, Esteller M. Epigenetic modifications and human disease. Nat Biotechnol 2010;28(10):1057-68
  • Liu G, Mattick JS, Taft RJ. A meta-analysis of the genomic and transcriptomic composition of complex life. Cell cycle 2013;12(13):2061-72
  • Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 1993;75(5):843-54
  • Flynt AS, Lai EC. Biological principles of microRNA-mediated regulation: shared themes amid diversity. Nat Rev Genet 2008;9(11):831-42
  • Turchinovich A, Weiz L, Langheinz A, Burwinkel B. Characterization of extracellular circulating microRNA. Nucleic Acids Res 2011;39(16):7223-33
  • Arroyo JD, Chevillet JR, Kroh EM, et al. Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma. Proc Natl Acad Sci USA 2011;108(12):5003-8
  • Oak SR, Murray L, Herath A, et al. A micro RNA processing defect in rapidly progressing idiopathic pulmonary fibrosis. PLoS ONE 2011;6(6):e21253
  • Honeyman L, Bazett M, Tomko TG, Haston CK. MicroRNA profiling implicates the insulin-like growth factor pathway in bleomycin-induced pulmonary fibrosis in mice. Fibrog Tissue Repair 2013;6(1):16
  • Babalola O, Mamalis A, Lev-Tov H, Jagdeo J. The role of microRNAs in skin fibrosis. Arch Dermatol Res 2013;305(9):763-76
  • Zhu H, Li Y, Qu S, et al. MicroRNA expression abnormalities in limited cutaneous scleroderma and diffuse cutaneous scleroderma. J Clin Immunol 2012;32(3):514-22
  • Liu G, Friggeri A, Yang Y, et al. miR-21 mediates fibrogenic activation of pulmonary fibroblasts and lung fibrosis. J Exp Med 2010;207(8):1589-97
  • Yamada M, Kubo H, Ota C, et al. The increase of microRNA-21 during lung fibrosis and its contribution to epithelial-mesenchymal transition in pulmonary epithelial cells. Respir Res 2013;14:95
  • Lino Cardenas CL, Henaoui IS, Courcot E, et al. miR-199a-5p Is upregulated during fibrogenic response to tissue injury and mediates TGFbeta-induced lung fibroblast activation by targeting caveolin-1. PLoS Genet 2013;9(2):e1003291
  • Yang S, Cui H, Xie N, et al. miR-145 regulates myofibroblast differentiation and lung fibrosis. FASEB J 2013;27(6):2382-91
  • Milosevic J, Pandit K, Magister M, et al. Profibrotic role of miR-154 in pulmonary fibrosis. Am J Respir Cell Mol Biol 2012;47(6):879-87
  • Wang Y, Huang C, Reddy CN, et al. miR-375 regulates rat alveolar epithelial cell trans-differentiation by inhibiting Wnt/beta-catenin pathway. Nucleic Acids Res 2013;41(6):3833-44
  • Pandit KV, Corcoran D, Yousef H, et al. Inhibition and role of let-7d in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2010;182(2):220-9
  • Yang S, Banerjee S, de Freitas A, et al. Participation of miR-200 in pulmonary fibrosis. Am J Pathol 2012;180(2):484-93
  • Dakhlallah D, Batte K, Wang Y, et al. Epigenetic regulation of miR-17∼92 contributes to the pathogenesis of pulmonary fibrosis. Am J Respir Crit Care Med 2013;187(4):397-405
  • Cushing L, Kuang P, Lu J. The role of miR-29 in pulmonary fibrosis. Biochem Cell Biol 2015;93(2):109-18
  • Maurer B, Stanczyk J, Jungel A, et al. MicroRNA-29, a key regulator of collagen expression in systemic sclerosis. Arthritis Rheum 2010;62(6):1733-43
  • Zhang H, Liu X, Chen S, et al. Tectorigenin inhibits the in vitro proliferation and enhances miR-338* expression of pulmonary fibroblasts in rats with idiopathic pulmonary fibrosis. J Ethnopharmacol 2010;131(1):165-73
  • Crouser ED, Julian MW, Crawford M, et al. Differential expression of microRNA and predicted targets in pulmonary sarcoidosis. Biochem Biophys Res Commun 2012;417(2):886-91
  • Maertzdorf J, Weiner JIII, Mollenkopf HJ, et al. Common patterns and disease-related signatures in tuberculosis and sarcoidosis. Proc Natl Acad Sci USA 2012;109(20):7853-8
  • Jazwa A, Kasper L, Bak M, et al. Differential inflammatory microRNA and cytokine expression in pulmonary sarcoidosis. Arch Immunol Ther Exp (Warsz) 2015;63(2):139-46
  • Ji P, Diederichs S, Wang W, et al. MALAT-1, a novel noncoding RNA, and thymosin beta4 predict metastasis and survival in early-stage non-small cell lung cancer. Oncogene 2003;22(39):8031-41
  • Song X, Cao G, Jing L, et al. Analysing the relationship between lncRNA and protein-coding gene and the role of lncRNA as ceRNA in pulmonary fibrosis. J Cell Mol Med 2014;18(6):991-1003
  • Cho JH, Gelinas R, Wang K, et al. Systems biology of interstitial lung diseases: integration of mRNA and microRNA expression changes. BMC Med Genomics 2011;4:8
  • Ohnishi H, Yokoyama A, Kondo K, et al. Comparative study of KL-6, surfactant protein-A, surfactant protein-D, and monocyte chemoattractant protein-1 as serum markers for interstitial lung diseases. Am J Respir Crit Care Med 2002;165(3):378-81
  • Asano Y, Ihn H, Yamane K, et al. Clinical significance of surfactant protein D as a serum marker for evaluating pulmonary fibrosis in patients with systemic sclerosis. Arthritis Rheum 2001;44(6):1363-9
  • Arai S, Kurasawa K, Maezawa R, 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(5):872-83
  • Yokoyama A, Kondo K, Nakajima M, et al. Prognostic value of circulating KL-6 in idiopathic pulmonary fibrosis. Respirology 2006;11(2):164-8
  • Yokoyama A, Kohno N, Hamada H, et al. Circulating KL-6 predicts the outcome of rapidly progressive idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 1998;158(5 Pt 1):1680-4
  • Takahashi T, Munakata M, Suzuki I, Kawakami Y. Serum and bronchoalveolar fluid KL-6 levels in patients with pulmonary alveolar proteinosis. Am J Respir Crit Care Med 1998;158(4):1294-8
  • Ohshimo S, Ishikawa N, Horimasu Y, et al. Baseline KL-6 predicts increased risk for acute exacerbation of idiopathic pulmonary fibrosis. Respir Med 2014;108(7):1031-9
  • Ohshimo S, Bonella F, Sommerwerck U, et al. Comparison of serum KL-6 versus bronchoalveolar lavage neutrophilia for the diagnosis of bronchiolitis obliterans in lung transplantation. J Heart Lung Transplant 2011;30(12):1374-80
  • Ohnishi H, Yokoyama A, Yasuhara Y, et al. Circulating KL-6 levels in patients with drug induced pneumonitis. Thorax 2003;58(10):872-5
  • Johansen JS, Milman N, Hansen M, et al. Increased serum YKL-40 in patients with pulmonary sarcoidosis–a potential marker of disease activity? Respir Med 2005;99(4):396-402
  • Furuhashi K, Suda T, Nakamura Y, et al. Increased expression of YKL-40, a chitinase-like protein, in serum and lung of patients with idiopathic pulmonary fibrosis. Respir Med 2010;104(8):1204-10
  • Okada M, Suzuki K, Nakanishi T, Nakashima M. Serum levels of KL-6 are positively correlated with those of CA15-3 in patients with interstitial pneumonia associated with collagen diseases. Respirology 2006;11(4):509-10
  • Kruit A, Gerritsen WB, Pot N, et al. CA 15-3 as an alternative marker for KL-6 in fibrotic lung diseases. Sarcoidosis Vasc Diffuse Lung Dis 2010;27(2):138-46
  • Ohashi K, Sato A, Takada T, et al. Direct evidence that GM-CSF inhalation improves lung clearance in pulmonary alveolar proteinosis. Respir Med 2012;106(2):284-93
  • Arai T, Inoue Y, Sugimoto C, et al. CYFRA 21-1 as a disease severity marker for autoimmune pulmonary alveolar proteinosis. Respirology 2014;19(2):246-52
  • Kanazawa H, Yoshikawa T, Yamada M, et al. CYFRA 21-1, a cytokeratin subunit 19 fragment, in bronchoalveolar lavage fluid from patients with interstitial lung disease. Clin Sci 1998;94(5):531-5
  • Nakayama M, Satoh H, Ishikawa H, et al. Cytokeratin 19 fragment in patients with nonmalignant respiratory diseases. Chest 2003;123(6):2001-6
  • Fujita J, Dobashi N, Tokuda M, et al. Elevation of cytokeratin 19 fragment in patients with interstitial pneumonia associated with polymyositis/dermatomyositis. J Rheumatol 1999;26(11):2377-82
  • Fujita J, Dobashi N, Ohtsuki Y, et al. Elevation of anti-cytokeratin 19 antibody in sera of the patients with idiopathic pulmonary fibrosis and pulmonary fibrosis associated with collagen vascular disorders. Lung 1999;177(5):311-19
  • Dobashi N, Fujita J, Ohtsuki Y, et al. Elevated serum and BAL cytokeratin 19 fragment in pulmonary fibrosis and acute interstitial pneumonia. Eur Respir J 1999;14(3):574-8
  • Totani Y, Saito Y, Miyachi H, et al. Clinical characterization of CA19-9 in patients with interstitial pneumonia showing pathological nonspecific interstitial pneumonia pattern. Nihon Kokyuki Gakkai Zasshi 2005;43(2):77-83
  • Totani Y, Demura Y, Ameshima S, et al. Serum CA19-9 levels reflect bronchoalveolar lavage fluid neutrophil levels in idiopathic pulmonary fibrosis. Respiration 2001;68(4):438
  • Obayashi Y, Fujita J, Nishiyama T, et al. Role of carbohydrate antigens sialyl Lewis (a) (CA19-9) in bronchoalveolar lavage in patients with pulmonary fibrosis. Respiration 2000;67(2):146-52
  • Hirakata Y, Kobayashi J, Sugama Y, Kitamura S. Elevation of tumour markers in serum and bronchoalveolar lavage fluid in pulmonary alveolar proteinosis. Eur Respir J 1995;8(5):689-96
  • Fujita J, Obayashi Y, Yamadori I, et al. Marked elevation of CA19-9 in a patient with idiopathic pulmonary fibrosis: CA19-9 as a bad prognostic factor. Respirology 1998;3(3):211-14
  • Satoh H, Kamma H, Ogata T, et al. Clinical significance of serum levels of a carbohydrate antigen, sialyl SSEA-1, in patients with fibrosing lung disease. Am Rev Respir Dis 1991;144(5):1177-81
  • Mukae H, Hirota M, Kohno S, et al. Elevation of tumor-associated carbohydrate antigens in patients with diffuse panbronchiolitis. Am Rev Respir Dis 1993;148(3):744-51
  • Mukae H, Ishimoto H, Yanagi S, et al. Elevated BALF concentrations of alpha- and beta-defensins in patients with pulmonary alveolar proteinosis. Respir Med 2007;101(4):715-21
  • Mukae H, Iiboshi H, Nakazato M, et al. Raised plasma concentrations of alpha-defensins in patients with idiopathic pulmonary fibrosis. Thorax 2002;57(7):623-8
  • Ashitani J, Mukae H, Nakazato M, et al. Elevated concentrations of defensins in bronchoalveolar lavage fluid in diffuse panbronchiolitis. Eur Respir J 1998;11(1):104-11
  • Hiratsuka T, Mukae H, Iiboshi H, et al. Increased concentrations of human beta-defensins in plasma and bronchoalveolar lavage fluid of patients with diffuse panbronchiolitis. Thorax 2003;58(5):425-30
  • Sakamoto N, Ishimatsu Y, Kakugawa T, et al. Elevated plasma alpha-defensins in patients with acute exacerbation of fibrotic interstitial pneumonia. Respir Med 2015;109(2):265-71
  • Bargagli E, Bianchi N, Margollicci M, et al. Chitotriosidase and soluble IL-2 receptor: comparison of two markers of sarcoidosis severity. Scand J Clin Lab Invest 2008;68(6):479-83
  • Pantelidis P, Fanning GC, Wells AU, et al. Analysis of tumor necrosis factor-alpha, lymphotoxin-alpha, tumor necrosis factor receptor II, and interleukin-6 polymorphisms in patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2001;163(6):1432-6
  • Ryerson CJ, Collard HR. How to build a biomarker: IL-7 and acute exacerbation of IPF. Sarcoidosis Vasc Diffuse Lung Dis 2011;28(2):83-4
  • Cui A, Anhenn O, Theegarten D, et al. Angiogenic and angiostatic chemokines in idiopathic pulmonary fibrosis and granulomatous lung disease. Respiration 2010;80(5):372-8
  • Gourh P, Arnett FC, Assassi S, et al. Plasma cytokine profiles in systemic sclerosis: associations with autoantibody subsets and clinical manifestations. Arthr Res Ther 2009;11(5):R147
  • Baraut J, Michel L, Verrecchia F, Farge D. Relationship between cytokine profiles and clinical outcomes in patients with systemic sclerosis. Autoimmun Rev 2010;10(2):65-73
  • Antoniou KM, Tzortzaki EG, Alexandrakis MG, et al. Investigation of IL-18 and IL-12 in induced sputum of patients with IPF before and after treatment with interferon gamma-1b. Sarcoidosis Vasc Diffuse Lung Dis 2005;22(3):204-9
  • Murray LA, Zhang H, Oak SR, et al. Targeting interleukin-13 with tralokinumab attenuates lung fibrosis and epithelial damage in a humanized SCID idiopathic pulmonary fibrosis model. Am J Respir Cell Mol Biol 2014;50(5):985-94
  • Jakubzick C, Kunkel SL, Puri RK, Hogaboam CM. Therapeutic targeting of IL-4- and IL-13-responsive cells in pulmonary fibrosis. Immunol Res 2004;30(3):339-49
  • Truchetet ME, Brembilla NC, Montanari E, et al. Increased frequency of circulating Th22 in addition to Th17 and Th2 lymphocytes in systemic sclerosis: association with interstitial lung disease. Arthr Res Ther 2011;13(5):R166
  • Prior C, Haslam PL. In vivo levels and in vitro production of interferon-gamma in fibrosing interstitial lung diseases. Clin Exp Immunol 1992;88(2):280-7
  • Robinson BW, Rose AH. Pulmonary gamma interferon production in patients with fibrosing alveolitis. Thorax 1990;45(2):105-8
  • Wolff H, Teppo AM, Mutanen P, et al. Studies of cytokine levels in bronchoalveolar fluid lavage from patients with interstitial lung diseases. Scand J Clin Lab Invest 2003;63(1):27-36
  • Kusugami K, Ando T, Ohsuga M, et al. Mucosal chemokine activity in Helicobacter pylori infection. J Clin Gastroenterol 1997;25(Suppl 1):S203-10
  • Suga M, Iyonaga K, Ichiyasu H, et al. Clinical significance of MCP-1 levels in BALF and serum in patients with interstitial lung diseases. Eur Respir J 1999;14(2):376-82
  • Shinoda H, Tasaka S, Fujishima S, et al. Elevated CC chemokine level in bronchoalveolar lavage fluid is predictive of a poor outcome of idiopathic pulmonary fibrosis. Respiration 2009;78(3):285-92
  • Cui A, Bonella F, Ohshimo S, et al. Different levels of the chemokine CCL18 in bronchoalveolar lavage of patients with interstitial lung disease. Am J Respir Crit Med 2009;179:A2177
  • Yogo Y, Fujishima S, Inoue T, et al. Macrophage derived chemokine (CCL22), thymus and activation-regulated chemokine (CCL17), and CCR4 in idiopathic pulmonary fibrosis. Respir Res 2009;10:80
  • Sfriso P, Cozzi F, Oliviero F, et al. CXCL11 in bronchoalveolar lavage fluid and pulmonary function decline in systemic sclerosis. Clin Exp Rheumatol 2012;30(2 Suppl 71):S71-5
  • Antoniou KM, Soufla G, Proklou A, et al. Different activity of the biological axis VEGF-Flt-1 (fms-like tyrosine kinase 1) and CXC chemokines between pulmonary sarcoidosis and idiopathic pulmonary fibrosis: a bronchoalveolar lavage study. Clin Develop Immunol 2009;2009:537929
  • Lin FC, Chen YC, Chang SC. Clinical importance of bronchoalveolar lavage fluid and blood cytokines, surfactant protein D, and Kerbs von Lungren 6 antigen in idiopathic pulmonary alveolar proteinosis. Mayo Clin Proc 2008;83(12):1344-9
  • Azab NA, Rady HM, Marzouk SA. Elevated serum TRAIL levels in scleroderma patients and its possible association with pulmonary involvement. Clin Rheumatol 2012;31(9):1359-64
  • Matsushita T, Hasegawa M, Yanaba K, et al. Elevated serum BAFF levels in patients with systemic sclerosis: enhanced BAFF signaling in systemic sclerosis B lymphocytes. Arthritis Rheum 2006;54(1):192-201
  • Kurne A, Guc D, Canpinar H, et al. Analysis of BAFF and TRAIL expression levels in multiple sclerosis patients: evaluation of expression under immunomodulatory therapy. Acta Neurol Scand 2011;123(1):8-12
  • Leeming DJ, Sand JM, Nielsen MJ, et al. Serological investigation of the collagen degradation profile of patients with chronic obstructive pulmonary disease or idiopathic pulmonary fibrosis. Biomark Insights 2012;7:119-26
  • Kasuga I, Yonemaru M, Kiyokawa H, et al. Clinical evaluation of serum type IV collagen 7S in idiopathic pulmonary fibrosis. Respirology 1996;1(4):277-81
  • Bauer Y, Tedrow J, de Bernard S, et al. A novel genomic signature with translational significance for human idiopathic pulmonary fibrosis. Am J Respir Cell Mol Biol 2015;52(2):217-31
  • Konishi K, Gibson KF, Lindell KO, et al. Gene expression profiles of acute exacerbations of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2009;180(2):167-75
  • Richards TJ, Park C, Chen Y, et al. Allele-specific transactivation of matrix metalloproteinase 7 by FOXA2 and correlation with plasma levels in idiopathic pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol 2012;302(8):L746-54
  • Beeh KM, Beier J, Kornmann O, Buhl R. Sputum matrix metalloproteinase-9, tissue inhibitor of metalloprotinease-1, and their molar ratio in patients with chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis and healthy subjects. Respir Med 2003;97(6):634-9
  • Fujishima S, Shiomi T, Yamashita S, et al. Production and activation of matrix metalloproteinase 7 (matrilysin 1) in the lungs of patients with idiopathic pulmonary fibrosis. Arch Pathol Lab Med 2010;134(8):1136-42
  • Iwata Y, Yoshizaki A, Ogawa F, et al. Increased serum pentraxin 3 in patients with systemic sclerosis. J Rheumatol 2009;36(5):976-83
  • Diamond JM, Lederer DJ, Kawut SM, et al. Elevated plasma long pentraxin-3 levels and primary graft dysfunction after lung transplantation for idiopathic pulmonary fibrosis. Am J Transpl 2011;11(11):2517-22
  • Duffield JS, Lupher MLJr. PRM-151 (recombinant human serum amyloid P/pentraxin 2) for the treatment of fibrosis. Drug News Perspect 2010;23(5):305-15
  • Liu X, Mayes MD, Pedroza C, et al. Does C-reactive protein predict the long-term progression of interstitial lung disease and survival in patients with early systemic sclerosis? Arthr Care Res 2013;65(8):1375-80
  • Muangchan C, Harding S, Khimdas S, et al. Association of C-reactive protein with high disease activity in systemic sclerosis: results from the Canadian Scleroderma Research Group. Arthr Care Res 2012;64(9):1405-14
  • Berlin M, Lundahl J, Skold CM, et al. The lymphocytic alveolitis in sarcoidosis is associated with increased amounts of soluble and cell-bound adhesion molecules in bronchoalveolar lavage fluid and serum. J Intern Med 1998;244(4):333-40
  • Cipriani P, Di Benedetto P, Capece D, et al. Impaired Cav-1 expression in SSc mesenchymal cells upregulates VEGF signaling: a link between vascular involvement and fibrosis. Fibrogen Tissue Repair 2014;7:13
  • Ahmadzai H, Cameron B, Chui J, et al. Measurement of neopterin, TGF-beta1 and ACE in the exhaled breath condensate of patients with sarcoidosis. J Breath Res 2013;7(4):046003
  • Hyldgaard C, Kaae S, Riddervold M, et al. Value of s-ACE, BAL lymphocytosis, and CD4+/CD8+ and CD103+CD4+/CD4+ T-cell ratios in diagnosis of sarcoidosis. Eur Respir J 2012;39(4):1037-9
  • Danilov SM, Balyasnikova IV, Danilova AS, et al. Conformational fingerprinting of the angiotensin I-converting enzyme (ACE). 1. Application in sarcoidosis. J Proteome Res 2010;9(11):5782-93
  • Lieberman J. Enzymes in sarcoidosis. Angiotensin-converting-enzyme (ACE). Clin Lab Med 1989;9(4):745-55
  • Hesselstrand R, Wildt M, Bozovic G, 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
  • Bargagli E, Maggiorelli C, Rottoli P. Human chitotriosidase: a potential new marker of sarcoidosis severity. Respiration 2008;76(2):234-8
  • Bargagli E, Margollicci M, Luddi A, et al. Chitotriosidase activity in patients with interstitial lung diseases. Respir Med 2007;101(10):2176-81
  • Bargagli E, Rottoli P. Serum chitotriosidase activity in sarcoidosis patients. Rheumatol Int 2007;27(12):1187
  • Grosso S, Margollicci MA, Bargagli E, et al. Serum levels of chitotriosidase as a marker of disease activity and clinical stage in sarcoidosis. Scand J Clin Lab Invest 2004;64(1):57-62
  • Harlander M, Salobir B, Zupancic M, et al. Serial chitotriosidase measurements in sarcoidosis–two to five year follow-up study. Respir Med 2014;108(5):775-82
  • Seymour JF, Doyle IR, Nakata K, et al. Relationship of anti-GM-CSF antibody concentration, surfactant protein A and B levels, and serum LDH to pulmonary parameters and response to GM-CSF therapy in patients with idiopathic alveolar proteinosis. Thorax 2003;58(3):252-7
  • Kottmann RM, Kulkarni AA, Smolnycki KA, et al. Lactic acid is elevated in idiopathic pulmonary fibrosis and induces myofibroblast differentiation via pH-dependent activation of transforming growth factor-beta. Am J Respir Crit Care Med 2012;186(8):740-51
  • Hoffman RM, Rogers RM. Serum and lavage lactate dehydrogenase isoenzymes in pulmonary alveolar proteinosis. Am Rev Respir Dis 1991;143(1):42-6
  • Matusiewicz SP, Williamson IJ, Sime PJ, et al. Plasma lactate dehydrogenase: a marker of disease activity in cryptogenic fibrosing alveolitis and extrinsic allergic alveolitis? Eur Respir J 1993;6(9):1282-6
  • Bargagli E, Olivieri C, Nikiforakis N, et al. Analysis of macrophage migration inhibitory factor (MIF) in patients with idiopathic pulmonary fibrosis. Respir Physiol Neurobiol 2009;167(3):261-7
  • Planck A, Eklund A, Grunewald J. Markers of activity in clinically recovered human leukocyte antigen-DR17-positive sarcoidosis patients. Eur Respir J 2003;21(1):52-7
  • Barizzone N, Marchini M, Cappiello F, et al. Association of osteopontin regulatory polymorphisms with systemic sclerosis. Hum Immunol 2011;72(10):930-4
  • Kono M, Nakamura Y, Suda T, et al. Plasma CCN2 (connective tissue growth factor; CTGF) is a potential biomarker in idiopathic pulmonary fibrosis (IPF). Clinica Chimica Acta 2011;412(23-24):2211-15
  • Sato S, Nagaoka T, Hasegawa M, et al. Serum levels of connective tissue growth factor are elevated in patients with systemic sclerosis: association with extent of skin sclerosis and severity of pulmonary fibrosis. J Rheumatol 2000;27(1):149-54
  • Dziadzio M, Usinger W, Leask A, et al. N-terminal connective tissue growth factor is a marker of the fibrotic phenotype in scleroderma. QJM 2005;98(7):485-92
  • Fernandez IE, Eickelberg O. The impact of TGF-beta on lung fibrosis: from targeting to biomarkers. Proc Am Thorac Soc 2012;9(3):111-16
  • Amenomori M, Mukae H, Sakamoto N, et al. HSP47 in lung fibroblasts is a predictor of survival in fibrotic nonspecific interstitial pneumonia. Respir Med 2010;104(6):895-901
  • Kakugawa T, Yokota S, Mukae H, et al. High serum concentrations of autoantibodies to HSP47 in nonspecific interstitial pneumonia compared with idiopathic pulmonary fibrosis. BMC Pulm Med 2008;8:23
  • Kakugawa T, Yokota S, Ishimatsu Y, et al. Serum heat shock protein 47 levels in patients with drug-induced lung disease. Respir Res 2013;14:133
  • Kakugawa T, Yokota S, Ishimatsu Y, et al. Serum heat shock protein 47 levels are elevated in acute interstitial pneumonia. BMC Pulm Med 2014;14:48
  • Kakugawa T, Yokota S, Ishimatsu Y, et al. Serum heat shock protein 47 levels are elevated in acute exacerbation of idiopathic pulmonary fibrosis. Cell Stress Chaperones 2013;18(5):581-90
  • Takemoto R, Jinnin M, Wang Z, et al. Hair miR-29a levels are decreased in patients with scleroderma. Exp Dermatol 2013;22(12):832-3
  • Nakashima T, Jinnin M, Yamane K, et al. Impaired IL-17 signaling pathway contributes to the increased collagen expression in scleroderma fibroblasts. J Immunol 2012;188(8):3573-83
  • Etoh M, Jinnin M, Makino K, et al. microRNA-7 down-regulation mediates excessive collagen expression in localized scleroderma. Arch Dermatol Res 2013;305(1):9-15
  • Makino K, Jinnin M, Hirano A, et al. The downregulation of microRNA let-7a contributes to the excessive expression of type I collagen in systemic and localized scleroderma. J Immunol 2013;190(8):3905-15
  • Sing T, Jinnin M, Yamane K, et al. microRNA-92a expression in the sera and dermal fibroblasts increases in patients with scleroderma. Rheumatology (Oxford) 2012;51(9):1550-6
  • Makino K, Jinnin M, Kajihara I, et al. Circulating miR-142-3p levels in patients with systemic sclerosis. Clin Exp Dermatol 2012;37(1):34-9
  • Honda N, Jinnin M, Kira-Etoh T, et al. miR-150 down-regulation contributes to the constitutive type I collagen overexpression in scleroderma dermal fibroblasts via the induction of integrin beta3. Am J Pathol 2013;182(1):206-16
  • Honda N, Jinnin M, Kajihara I, et al. TGF-beta-mediated downregulation of microRNA-196a contributes to the constitutive upregulated type I collagen expression in scleroderma dermal fibroblasts. J Immunol 2012;188(7):3323-31
  • Wang Z, Jinnin M, Kudo H, et al. Detection of hair-microRNAs as the novel potent biomarker: evaluation of the usefulness for the diagnosis of scleroderma. J Dermatol Sci 2013;72(2):134-41

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.