Blood Biomarkers in Idiopathic Pulmonary Fibrosis.

[en] PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease of unknown origin whose incidence has been increasing over the latest decade partly as a consequence of population ageing. New anti-fibrotic therapy including pirfenidone and nintedanib have now proven efficacy in slowing down the disease. Nevertheless, diagnosis and follow-up of IPF remain challenging. METHODS: This review examines the recent literature on potentially useful blood molecular and cellular biomarkers in IPF. Most of the proposed biomarkers belong to chemokines (IL-8, CCL18), proteases (MMP-1 and MMP-7), and growth factors (IGBPs) families. Circulating T cells and fibrocytes have also gained recent interest in that respect. Up to now, though several interesting candidates are profiling there has not been a single biomarker, which proved to be specific of the disease and predictive of the evolution (decline of pulmonary function test values, risk of acute exacerbation or mortality). CONCLUSION: Large scale multicentric studies are eagerly needed to confirm the utility of these biomarkers.

Disciplines :

Cardiovascular & respiratory systems

Author, co-author :

GUIOT, Julien ; Centre Hospitalier Universitaire de Liège - CHU > Service de pneumologie - allergologie

Moermans, Catherine ; Centre Hospitalier Universitaire de Liège - CHU > Service de pneumologie - allergologie

HENKET, Monique ; Université de Liège > Département des sciences cliniques > Département des sciences cliniques

Corhay, Jean-Louis ; Université de Liège > Département des sciences cliniques > Pneumologie - Allergologie

Louis, Renaud

Language :

English

Title :

Blood Biomarkers in Idiopathic Pulmonary Fibrosis.

Publication date :

28 March 2017

Journal title :

Lung

ISSN :

0341-2040

eISSN :

1432-1750

Publisher :

Springer, Germany

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

http://link.springer.com/article/10.1007%2Fs00408-017-9993-5

Available on ORBi :

since 11 May 2017

Statistics

Number of views

188 (20 by ULiège)

Number of downloads

194 (9 by ULiège)

More statistics

Scopus citations^®

104

Scopus citations^®
without self-citations

OpenCitations

OpenAlex citations

124

Bibliography

Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK et al (2011) An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med 183(6):788–824
Raghu G, Weycker D, Edelsberg J, Bradford WZ, Oster G (2006) Incidence and prevalence of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 174(7):810–816
King TE, Bradford WZ, Castro-Bernardini S, Fagan EA, Glaspole I, Glassberg MK et al (2014) A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med 370(22):2083–2092
Richeldi L, du Bois RM, Raghu G, Azuma A, Brown KK, Costabel U et al (2014) Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med 370(22):2071–2082
Maher TM (2013) PROFILEing idiopathic pulmonary fibrosis: rethinking biomarker discovery. Eur Respir Rev 22(128):148–152
Kaarteenaho R, Lappi-Blanco E (2015) Tissue is an issue in the search for biomarkers in idiopathic pulmonary fibrosis. Fibrogenesis Tissue Repair 8(1):3
Zhang Y, Kaminski N (2012) Biomarkers in idiopathic pulmonary fibrosis. Curr Opin Pulm Med 18(5):441–446
Raghu G, Rochwerg B, Zhang Y, Garcia CAC, Azuma A, Behr J et al (2015) An official ATS/ERS/JRS/ALAT clinical practice guideline: treatment of idiopathic pulmonary fibrosis. an update of the 2011 clinical practice guideline. Am J Respir Crit Care Med 192(2):e3–e19
Prasad R, Gupta N, Singh A, Gupta P (2015) Diagnosis of idiopathic pulmonary fibrosis: current issues. Intractable Rare Dis Res 4(2):65–69
Morell F, Villar A, Montero M-Á, Muñoz X, Colby TV, Pipvath S et al (2013) Chronic hypersensitivity pneumonitis in patients diagnosed with idiopathic pulmonary fibrosis: a prospective case-cohort study. Lancet Respir Med 1(9):685–694
Ohnishi H, Yokoyama A, Kondo K, Hamada H, Abe M, Nishimura K et al (2002) 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 165(3):378–381
Kobayashi J, Kitamura S (1995) KL-6: a serum marker for interstitial pneumonia. Chest 108(2):311–315
Furuhashi K, Suda T, Nakamura Y, Inui N, Hashimoto D, Miwa S et al (2010) Increased expression of YKL-40, a chitinase-like protein, in serum and lung of patients with idiopathic pulmonary fibrosis. Respir Med 104(8):1204–1210
Ohshimo S, Ishikawa N, Horimasu Y, Hattori N, Hirohashi N, Tanigawa K et al (2014) Baseline KL-6 predicts increased risk for acute exacerbation of idiopathic pulmonary fibrosis. Respir Med 108(7):1031–1039
Ishikawa N, Hattori N, Yokoyama A, Tanaka S, Nishino R, Yoshioka K et al (2008) Usefulness of monitoring the circulating Krebs von den Lungen-6 levels to predict the clinical outcome of patients with advanced nonsmall cell lung cancer treated with epidermal growth factor receptor tyrosine kinase inhibitors. Int J Cancer 122(11): 2612–2620
Hirasawa Y, Kohno N, Yokoyama A, Inoue Y, Abe M, Hiwada K (1997) KL-6, a human MUC1 mucin, is chemotactic for human fibroblasts. Am J Respir Cell Mol Biol 17(4):501–507
Ohshimo S, Yokoyama A, Hattori N, Ishikawa N, Hirasawa Y, Kohno N (2005) KL-6, a human MUC1 mucin, promotes proliferation and survival of lung fibroblasts. Biochem Biophys Res Commun 338(4): 1845–52
Satoh H, Kurishima K, Ishikawa H, Ohtsuka M (2006) Increased levels of KL-6 and subsequent mortality in patients with interstitial lung diseases. J Intern Med 260(5):429–434
Yokoyama A, Kohno N, Hamada H, Sakatani M, Ueda E, Kondo K et al (1998) Circulating KL-6 predicts the outcome of rapidly progressive idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 158(5 Pt 1):1680–1684
Guiot J, Bondue B, Henket M, Corhay JL, Louis R (2016) Raised serum levels of IGFBP-1 and IGFBP-2 in idiopathic pulmonary fibrosis. BMC Pulm Med 16(1):86
Ishii H, Mukae H, Kadota J, Kaida H, Nagata T, Abe K et al (2003) High serum concentrations of surfactant protein A in usual interstitial pneumonia compared with non-specific interstitial pneumonia. Thorax 58(1):52–57
Kohno N, Yokoyama A, Hirasawa Y, Kondo K, Fujino S, Abe M et al (1997) Comparative studies of circulating KL-6, type III procollagen N-terminal peptide and type IV collagen 7 S in patients with interstitial pneumonitis and alveolar pneumonia. Respir Med 91(9):558–561
Greene KE, King TE, Kuroki Y, Bucher-Bartelson B, Hunninghake GW, Newman LS et al (2002) Serum surfactant proteins-A and -D as biomarkers in idiopathic pulmonary fibrosis. Eur Respir J 19(3):439–446
Kinder BW, Brown KK, McCormack FX, Ix JH, Kervitsky A, Schwarz MI et al (2009) Serum surfactant protein-A is a strong predictor of early mortality in idiopathic pulmonary fibrosis. Chest 135(6):1557–1563
Barlo NP, van Moorsel CHM, Ruven HJT, Zanen P, van den Bosch JMM, Grutters JC (2009) Surfactant protein-D predicts survival in patients with idiopathic pulmonary fibrosis. Sarcoidosis Vasc Diffus lung Dis 26(2):155–161
Vázquez de Lara L, Becerril C, Montaño M, Ramos C, Maldonado V, Meléndez J et al (2000) Surfactant components modulate fibroblast apoptosis and type I collagen and collagenase-1 expression. Am J Physiol Lung Cell Mol Physiol 279(5):L950–L957
Takahashi H, Fujishima T, Koba H, Murakami S, Kurokawa K, Shibuya Y et al (2000) Serum surfactant proteins A and D as prognostic factors in idiopathic pulmonary fibrosis and their relationship to disease extent. Am J Respir Crit Care Med 162(3 Pt 1):1109–1114
van Moorsel CHM, van Oosterhout MFM, Barlo NP, de Jong PA, van der Vis JJ, Ruven HJT et al (2010) Surfactant protein C mutations are the basis of a significant portion of adult familial pulmonary fibrosis in a dutch cohort. Am J Respir Crit Care Med 182(11):1419–1425
Oikonomidi S, Kostikas K, Tsilioni I, Tanou K, Gourgoulianis KI, Kiropoulos TS (2009) Matrix metalloproteinases in respiratory diseases: from pathogenesis to potential clinical implications. Curr Med Chem 16(10):1214–1228
Rosas IO, Richards TJ, Konishi K, Zhang Y, Gibson K, Lokshin AE et al (2008) MMP1 and MMP7 as potential peripheral blood biomarkers in idiopathic pulmonary fibrosis. PLoS Med 5(4):e93
Vij R, Noth I (2012) Peripheral blood biomarkers in idiopathic pulmonary fibrosis. Transl Res 159(4):218–227
Dancer RCA, Wood AM, Thickett DR (2011) Metalloproteinases in idiopathic pulmonary fibrosis. Eur Respir J 38(6):1461–1467
Fujishima S, Shiomi T, Yamashita S, Yogo Y, Nakano Y, Inoue T et al (2010) Production and activation of matrix metalloproteinase 7 (matrilysin 1) in the lungs of patients with idiopathic pulmonary fibrosis. Arch Pathol Lab Med 134(8):1136–1142
Jenkins RG, Simpson JK, Saini G, Bentley JH, Russell A-M, Braybrooke R et al (2015) Longitudinal change in collagen degradation biomarkers in idiopathic pulmonary fibrosis: an analysis from the prospective, multicentre PROFILE study. Lancet. Respir Med 3(6):462–472
Chien J, Shao L, Lyman S, Adamkewicz J, Smith V, O’Riordan T (2014) Elevated serum LOXL2 levels are associated with rapid disease progression in idiopathic pulmonary fibrosis (IPF). Eur Respir J 40(Suppl 56)
Chien JW, Richards TJ, Gibson KF, Zhang Y, Lindell KO, Shao L et al(2014) Serum lysyl oxidase-like 2 levels and idiopathic pulmonary fibrosis disease progression. Eur Respir J 43(5):1430–1438
Patrick O’Brien (2016) Gilead Terminates Phase 2 Study of Simtuzumab in Patients With Idiopathic Pulmonary Fibrosis | Gilead [Internet]. Available from: http://www.gilead.com/news/press-releases/2016/1/gilead-terminates-phase-2-study-of-simtuzumab-in-patients-with-idiopathic-pulmonary-fibrosis
Okamoto M, Hoshino T, Kitasato Y, Sakazaki Y, Kawayama T, Fujimoto K et al (2011) Periostin, a matrix protein, is a novel biomarker for idiopathic interstitial pneumonias. Eur Respir J 37(5):1119–1127
Naik PK, Bozyk PD, Bentley JK, Popova AP, Birch CM, Wilke CA et al(2012) Periostin promotes fibrosis and predicts progression in patients with idiopathic pulmonary fibrosis. AJP Lung Cell Mol Physiol 303(12):L1046–L1056
Hieshima K, Imai T, Baba M, Shoudai K, Ishizuka K, Nakagawa T et al (1997) A novel human CC chemokine PARC that is most homologous to macrophage-inflammatory protein-1 alpha/LD78 alpha and chemotactic for T lymphocytes, but not for monocytes. J Immunol 159(3):1140–1149
Prasse A, Pechkovsky D V, Toews GB, Jungraithmayr W, Kollert F, Goldmann T et al (2006) A vicious circle of alveolar macrophages and fibroblasts perpetuates pulmonary fibrosis via CCL18. Am J Respir Crit Care Med 173(7):781–792
Prasse A, Pechkovsky DV, Toews GB, Schäfer M, Eggeling S, Ludwig C et al (2007) CCL18 as an indicator of pulmonary fibrotic activity in idiopathic interstitial pneumonias and systemic sclerosis. Arthritis Rheum 56(5):1685–1693
Luzina IG, Tsymbalyuk N, Choi J, Hasday JD, Atamas SP (2006) CCL18-stimulated upregulation of collagen production in lung fibroblasts requires Sp1 signaling and basal Smad3 activity. J Cell Physiol 206(1):221–228
Prasse A, Probst C, Bargagli E, Zissel G, Toews GB, Flaherty KR et al (2009) Serum CC-Chemokine ligand 18 concentration predicts outcome in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 179(8):717–723
Saito Y, Azuma A, Matsuda K, Kamio K, Abe S, Gemma A (2016) Pirfenidone exerts a suppressive effect on CCL18 expression in U937-derived macrophages partly by inhibiting STAT6 phosphorylation. Immunopharmacol Immunotoxicol 38(6):464–71
Tsoutsou PG, Gourgoulianis KI, Petinaki E, Germenis A, Tsoutsou AG, Mpaka M et al (2006) Cytokine levels in the sera of patients with idiopathic pulmonary fibrosis. Respir Med 100(5):938–945
ZIEGENHAGEN MW, ZABEL P, ZISSEL G, SCHLAAK M, MÜLLER-QUERNHEIM J (1998) Serum level of interleukin 8 is elevated in idiopathic pulmonary fibrosis and indicates disease activity. Am J Respir Crit Care Med 157(3):762–768
Richards TJ, Kaminski N, Baribaud F, Flavin S, Brodmerkel C, Horowitz D et al (2012) Peripheral blood proteins predict mortality in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 185(1):67–76
Ober C, Chupp GL (2009) The chitinase and chitinase-like proteins: a review of genetic and functional studies in asthma and immune-mediated diseases. Curr Opin Allergy Clin Immunol 9(5):401–408
Létuvé S, Kozhich A, Arouche N, Grandsaigne M, Reed J, Dombret M-C et al (2008) YKL-40 is elevated in patients with chronic obstructive pulmonary disease and activates alveolar macrophages. J Immunol 181(7):5167–5173
Korthagen NM, van Moorsel CHM, Barlo NP, Ruven HJT, Kruit A, Heron M et al (2011) Serum and BALF YKL-40 levels are predictors of survival in idiopathic pulmonary fibrosis. Respir Med 105(1):106–113
Guiot J, Henket M, Corhay JL, Moermans C, Louis R (2017) Sputum biomarkers in IPF: Evidence for raised gene expression and protein level of IGFBP-2, IL-8 and MMP-7. PLoS ONE 12(2):e0171344.
Shijubo N, Imai K, Aoki S, Hirasawa M, Sugawara H, Koba H et al (1992) Circulating intercellular adhesion molecule-1 (ICAM-1) antigen in sera of patients with idiopathic pulmonary fibrosis. Clin Exp Immunol 89(1):58–62
Shijubo N, Imai K, Shigehara K, Hirasawa M, Tsujisaki M, Hinoda Y et al (1995) Soluble intercellular adhesion molecule-1 (ICAM-1) in sera and bronchoalveolar lavage (BAL) fluids of extrinsic allergic alveolitis. Clin Exp Immunol 102(1):91–97
Monacci WT, Merrill MJ, Oldfield EH (1993) Expression of vascular permeability factor/vascular endothelial growth factor in normal rat tissues. Am J Physiol 264(4 Pt 1):C995–C1002
Ando M, Miyazaki E, Ito T, Hiroshige S, Nureki S, Ueno T et al (2010) Significance of serum vascular endothelial growth factor level in patients with idiopathic pulmonary fibrosis. Lung 188(3):247–252.
Wollin L, Wex E, Pautsch A, Schnapp G, Hostettler KE, Stowasser S et al (2015) Mode of action of nintedanib in the treatment of idiopathic pulmonary fibrosis. Eur Respir J
Kahloon RA, Xue J, Bhargava A, Csizmadia E, Otterbein L, Kass DJ et al (2013) Patients with idiopathic pulmonary fibrosis with antibodies to heat shock protein 70 have poor prognoses. Am J Respir Crit Care Med 187(7):768–775
Jaffar J, Unger S, Corte TJ, Keller M, Wolters PJ, Richeldi L et al (2014) Fibulin-1 predicts disease progression in patients with idiopathic pulmonary fibrosis. Chest 146(4):1055–1063
Cao M, Swigris JJ, Wang X, Cao M, Qiu Y, Huang M et al (2016) Plasma leptin is elevated in acute exacerbation of idiopathic pulmonary fibrosis. Mediators Inflamm 2016:1–7
White ES, Xia M, Murray S, Dyal R, Flaherty CM, Flaherty KR et al (2016) Plasma surfactant protein-D, matrix metalloproteinase-7, and osteopontin index distinguishes idiopathic pulmonary fibrosis from other idiopathic interstitial pneumonias. Am J Respir Crit Care Med 194(10):1242–1251
Reilkoff RA, Peng H, Murray LA, Peng X, Russell T, Montgomery R et al (2013) Semaphorin 7a + regulatory T cells are associated with progressive idiopathic pulmonary fibrosis and are implicated in transforming growth factor-β1–induced pulmonary fibrosis. Am J Respir Crit Care Med 187(2):180–8
Gan Y, Reilkoff R, Peng X, Russell T, Chen Q, Mathai SK et al (2011) Role of semaphorin 7a signaling in transforming growth factor β1-induced lung fibrosis and scleroderma-related interstitial lung disease. Arthritis Rheum 63(8):2484–2494
Kang H-R, Lee CG, Homer RJ, Elias JA (2007) Semaphorin 7 A plays a critical role in TGF-β 1 –induced pulmonary fibrosis. J Exp Med 204(5):1083–1093
Gilani SR, Vuga LJ, Lindell KO, Gibson KF, Xue J, Kaminski N et al (2010) CD28 down-regulation on circulating CD4 T-cells is associated with poor prognoses of patients with idiopathic pulmonary fibrosis. PLoS ONE 5(1):e8959
Kotsianidis I, Nakou E, Bouchliou I, Tzouvelekis A, Spanoudakis E, Steiropoulos P et al (2009) Global impairment of CD4 + CD25 + FOXP3 + regulatory T cells in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 179(12):1121–1130
Vuga LJ, Tedrow JR, Pandit K V., Tan J, Kass DJ, Xue J et al (2014) C-X-C motif chemokine 13 (CXCL13) is a prognostic biomarker of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 189(8):966–974
Moeller A, Gilpin SE, Ask K, Cox G, Cook D, Gauldie J et al (2009) Circulating fibrocytes are an indicator of poor prognosis in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 179(7):588–594
Phillips RJ, Burdick MD, Hong K, Lutz MA, Murray LA, Xue YY et al (2004) Circulating fibrocytes traffic to the lungs in response to CXCL12 and mediate fibrosis. J Clin Invest 114(3):438–446
Mehrad B, Burdick MD, Zisman DA, Keane MP, Belperio JA, Strieter RM (2007) Circulating peripheral blood fibrocytes in human fibrotic interstitial lung disease. Biochem Biophys Res Commun 353(1):104–108
Daccord C, Maher TM (2016) Recent advances in understanding idiopathic pulmonary fibrosis. F1000Research 5
Makiguchi T, Yamada M, Yoshioka Y, Sugiura H, Koarai A, Chiba S et al (2016) Serum extracellular vesicular miR-21-5p is a predictor of the prognosis in idiopathic pulmonary fibrosis. Respir Res 17(1):110
Jiang X, Tsitsiou E, Herrick SE, Lindsay MA (2010) MicroRNAs and the regulation of fibrosis. FEBS J 277(9):2015–2021
Yokoyama A, Kondo K, Nakajima M, Matsushima T, Takahashi T, Nishimura M et al (2006) Prognostic value of circulating KL-6 in idiopathic pulmonary fibrosis. Respirology 11(2):164–168
Ley B, Brown KK, Collard HR (2014) Molecular biomarkers in idiopathic pulmonary fibrosis. AJP Lung Cell Mol Physiol 307(9):L681–L691
Spagnolo P, Tzouvelekis A, Maher TM (2015) Personalized medicine in idiopathic pulmonary fibrosis. Curr Opin Pulm Med 21(5):470–478
DePianto DJ, Chandriani S, Abbas AR, Jia G, N’Diaye EN, Caplazi P et al (2015) Heterogeneous gene expression signatures correspond to distinct lung pathologies and biomarkers of disease severity in idiopathic pulmonary fibrosis. Thorax 70(1):48–56
Herazo-Maya JD, Noth I, Duncan SR, Kim S, Ma S-F, Tseng GC et al (2013) Peripheral blood mononuclear cell gene expression profiles predict poor outcome in idiopathic pulmonary fibrosis. Sci Transl Med 5(205):205ra136–205ra136