Serum IGFBP-2 in systemic sclerosis as a prognostic factor of lung dysfunction.

Biomarkers; IGFBP2 protein, human; Insulin-Like Growth Factor Binding Protein 2; Adult; Aged; Disease Susceptibility; Female; Humans; Insulin-Like Growth Factor Binding Protein 2/blood; Lung Diseases, Interstitial/diagnosis; Lung Diseases, Interstitial/etiology; Male; Middle Aged; Prognosis; Respiratory Function Tests; Scleroderma, Systemic/blood; Scleroderma, Systemic/complications; Scleroderma, Systemic/diagnosis; Lung Diseases, Interstitial; Scleroderma, Systemic; Multidisciplinary

Abstract :

[en] Systemic sclerosis (SSc) is a rare connective tissue disease associated with rapid evolving interstitial lung disease (ILD), driving its mortality. Specific biomarkers associated with the progression of this lung disease are highly needed. We aimed to identify specific biomarkers of SSc-ILD to predict the evolution of the disease. For this, we compared prospectively serum levels of several biomarkers associated with lung fibrosis in SSc patients (n = 102), among which SSc-no ILD (n = 63) and SSc-ILD (n = 39), compared to healthy subjects (HS) (n = 39). We also performed a longitudinal study in a subgroup of 28 patients analyzing biomarkers variations and pulmonary function tests over a period of 2 years. Serum level of IGFBP-2 was significantly increased in SSc patients compared to HS, and negatively correlated with pulmonary function (assessed by carbon monoxide transfer coefficient (KCO)) (r = - 0.29, p < 0.01). Two-year longitudinal analysis in a subgroup of 28 SSc patients determined that IGFBP-2 variation was positively correlated with KCO at 2-year follow-up (r = 0.6, p < 0.001). SSc patients with a lower variation of IGFBP-2 (less than 22%) presented significant deterioration of pulmonary function at 2-year follow-up (p < 0.01). ROC curve analysis enabled us to identify that baseline IGFBP-2 > 105 ng/ml was associated with a poor outcome (KCO < 70% predicted) at 2-year follow-up (AUC = 0.75, p < 0.05). We showed for the first time that serum levels of IGFBP-2 might be a prognostic factor of the development of SSc-ILD.

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

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

NJOCK, Makon-Sébastien ; Centre Hospitalier Universitaire de Liège - CHU > > Service de rhumatologie ; Université de Liège - ULiège > GIGA > GIGA I3 - Pneumology

ANDRE, Béatrice ; Centre Hospitalier Universitaire de Liège - CHU > > Service de néphrologie

GESTER, Fanny ; Centre Hospitalier Universitaire de Liège - CHU > > Service de pneumologie - allergologie

HENKET, Monique ; Centre Hospitalier Universitaire de Liège - CHU > > Service de pneumologie - allergologie

DE SENY, Dominique ; Centre Hospitalier Universitaire de Liège - CHU > > Service de rhumatologie

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

MALAISE, Michel ; Centre Hospitalier Universitaire de Liège - CHU > > Service de rhumatologie

LOUIS, Renaud ; Centre Hospitalier Universitaire de Liège - CHU > > Service de pneumologie - allergologie

Language :

English

Title :

Serum IGFBP-2 in systemic sclerosis as a prognostic factor of lung dysfunction.

Publication date :

2021

Journal title :

Scientific Reports

eISSN :

2045-2322

Publisher :

Nature Research, England

Volume :

Issue :

Pages :

10882

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

http://www.nature.com/articles/s41598-021-90333-0.pdf

Available on ORBi :

since 17 March 2022

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Bibliography

Katsumoto, T. R., Whitfield, M. L. & Connolly, M. K. The pathogenesis of systemic sclerosis. Annu. Rev. Pathol. Mech. Dis. 6, 509–537 (2011). DOI: 10.1146/annurev-pathol-011110-130312
Caron, M., Hoa, S., Hudson, M., Schwartzman, K. & Steele, R. Pulmonary function tests as outcomes for systemic sclerosis interstitial lung disease. Eur. Respir. Rev. 27, 170102 (2018). DOI: 10.1183/16000617.0102-2017
van den Hoogen, F. et al. 2013 classification criteria for systemic sclerosis: An American college of rheumatology/European league against rheumatism collaborative initiative. Ann. Rheum. Dis. 72, 1747–1755 (2013). DOI: 10.1136/annrheumdis-2013-204424
Sánchez-Cano, D. et al. Interstitial lung disease in systemic sclerosis: Data from the Spanish scleroderma study group. Rheumatol. Int. 38, 363–374 (2018). DOI: 10.1007/s00296-017-3916-x
Schoenfeld, S. R. & Castelino, F. V. Interstitial lung disease in scleroderma. Rheum. Dis. Clin. N. Am. 41, 237–248 (2015). DOI: 10.1016/j.rdc.2014.12.005
Solomon, J. J. et al. Scleroderma lung disease. Eur. Respir. Rev. 22, 6–19 (2013). DOI: 10.1183/09059180.00005512
Steele, R., Hudson, M., Lo, E., Baron, M. & Canadian Scleroderma Research Group. Clinical decision rule to predict the presence of interstitial lung disease in systemic sclerosis. Arthritis Care Res. 64, 519–524 (2012). DOI: 10.1002/acr.21583
Steen, V. D. & Medsger, T. A. Changes in causes of death in systemic sclerosis, 1972–2002. Ann. Rheum. Dis. 66, 940–944 (2007). DOI: 10.1136/ard.2006.066068
Herzog, E. L. et al. Review: Interstitial lung disease associated with systemic sclerosis and idiopathic pulmonary fibrosis: How similar and distinct?. Arthritis Rheumatol. 66, 1967–1978 (2014). DOI: 10.1002/art.38702
Fastrès, A. et al. The lung microbiome in idiopathic pulmonary fibrosis: A promising approach for targeted therapies. Int. J. Mol. Sci. 18, 2735 (2017). DOI: 10.3390/ijms18122735
Guiot, J., Duysinx, B., Bonhomme, O., Louis, R. & Corhay, J.-L. How I treat a patient with idiopathic pulmonary fibrosis. Rev. Med. Liege 72, 381–383 (2017).
Guiot, J. et al. Altered epigenetic features in circulating nucleosomes in idiopathic pulmonary fibrosis. Clin. Epigenetics 9, 84 (2017). DOI: 10.1186/s13148-017-0383-x
McNearney, T. A. et al. Pulmonary involvement in systemic sclerosis: Associations with genetic, serologic, sociodemographic, and behavioral factors. Arthritis Rheumatol. 57, 318–326 (2007). DOI: 10.1002/art.22532
Guiot, J. et al. Clinical experience in idiopathic pulmonary fibrosis: A retrospective study. Acta Clin. Belg. Int. J. Clin. Lab. Med. 10.1080/17843286.2017.1399228 (2017). DOI: 10.1080/17843286.2017.1399228
Manno, R. & Boin, F. Immunotherapy of systemic sclerosis. Immunotherapy 2, 863–878 (2010). DOI: 10.2217/imt.10.69
Volkmann, E. R. & Varga, J. Emerging targets of disease-modifying therapy for systemic sclerosis. Nat. Rev. Rheumatol. 15, 208–224 (2019). DOI: 10.1038/s41584-019-0184-z
Worrell, J. C. & O’Reilly, S. Bi-directional communication: Conversations between fibroblasts and immune cells in systemic sclerosis. J. Autoimmun. 113, 102526 (2020). DOI: 10.1016/j.jaut.2020.102526
Njock, M.-S. et al. Sputum exosomes: Promising biomarkers for idiopathic pulmonary fibrosis. Thorax 74, 309–312 (2019). DOI: 10.1136/thoraxjnl-2018-211897
Bonhomme, O. et al. Biomarkers in systemic sclerosis-associated interstitial lung disease: Review of the literature. Rheumatology 61, 67–69 (2019).
Guiot, J., Moermans, C., Henket, M., Corhay, J.-L. & Louis, R. Blood biomarkers in idiopathic pulmonary fibrosis. Lung 195, 273–280 (2017). DOI: 10.1007/s00408-017-9993-5
Guiot, J. et al. Exosomal miRNAs in lung diseases: From biologic function to therapeutic targets. J. Clin. Med. 8, 1345 (2019). DOI: 10.3390/jcm8091345
Okano, Y. Antinuclear antibody in systemic sclerosis (scleroderma). Rheum. Dis. Clin. 22, 709–735 (1996). DOI: 10.1016/S0889-857X(05)70297-0
Steen, V. D. Autoantibodies in systemic sclerosis. Semin. Arthritis Rheum. 35, 35–42 (2005). DOI: 10.1016/j.semarthrit.2005.03.005
Castro, S. V. & Jimenez, S. A. Biomarkers in systemic sclerosis. Biomark. Med. 4, 133–147 (2010). DOI: 10.2217/bmm.09.79
Basu, D. & Reveille, J. D. Anti-scl-70. Autoimmunity 38, 65–72 (2005). DOI: 10.1080/08916930400022947
Kallenberg, C. G. Anti-centromere antibodies (ACA). Clin. Rheumatol. 9, 136–139 (1990). DOI: 10.1007/BF02205562
Asano, Y. et al. Clinical significance of surfactant protein D as a serum marker for evaluating pulmonary fibrosis in patients with systemic sclerosis. Arthritis Rheumatol. 44, 1363–1369 (2001). DOI: 10.1002/1529-0131(200106)44:6<1363::AID-ART229>3.0.CO;2-5
Takahashi, 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. 162, 258–263 (2000). DOI: 10.1164/ajrccm.162.1.9903014
Yamane, K. et al. Serum levels of KL-6 as a useful marker for evaluating pulmonary fibrosis in patients with systemic sclerosis. J. Rheumatol. 27, 930–934 (2000).
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. 31, 1112–1120 (2004).
Raghu, G. 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. 183, 788–824 (2011). DOI: 10.1164/rccm.2009-040GL
Godinas, L. et al. Increased production of TGF-β1 from sputum cells of COPD: Relationship with airway obstruction. Cytokine 99, 1–8 (2017). DOI: 10.1016/j.cyto.2017.06.018
Guiot, J., Bondue, B., Henket, M., Corhay, J. L. & Louis, R. Raised serum levels of IGFBP-1 and IGFBP-2 in idiopathic pulmonary fibrosis. BMC Pulm. Med. 16, 86 (2016). DOI: 10.1186/s12890-016-0249-6
Hirota, N., Ito, T., Miyazaki, S., Ebina, M. & Homma, S. Gene expression profiling of lung myofibroblasts reveals the anti-fibrotic effects of cyclosporine. Tohoku J. Exp. Med. 233, 283–293 (2014). DOI: 10.1620/tjem.233.283
Duan, C. & Xu, Q. Roles of insulin-like growth factor (IGF) binding proteins in regulating IGF actions. Gen. Comp. Endocrinol. 142, 44–52 (2005). DOI: 10.1016/j.ygcen.2004.12.022
Shimasaki, S. & Ling, N. Identification and molecular characterization of insulin-like growth factor binding proteins (IGFBP-1, -2, -3, -4, -5 and -6). Prog. Growth Factor Res. 3, 243–266 (1991). DOI: 10.1016/0955-2235(91)90003-M
Ding, H. & Wu, T. Insulin-like growth factor binding proteins in autoimmune diseases. Front. Endocrinol. 9, 499 (2018). DOI: 10.3389/fendo.2018.00499
Kim, H. S. et al. Identification of a family of low-affinity insulin-like growth factor binding proteins (IGFBPs): Characterization of connective tissue growth factor as a member of the IGFBP superfamily. Proc. Natl. Acad. Sci. U.S.A. 94, 12981–12986 (1997). DOI: 10.1073/pnas.94.24.12981
Chadelat, K. et al. Expression of insulin-like growth factors and their binding proteins by bronchoalveolar cells from children with and without interstitial lung disease. Eur. Respir. J. 11, 1329–1336 (1998). DOI: 10.1183/09031936.98.11061329
Guiot, J., Henket, M., Corhay, J. L., Moermans, C. & Louis, R. Sputum biomarkers in IPF: Evidence for raised gene expression and protein level of IGFBP-2, IL-8 and MMP-7. PLoS One 12, e0171344 (2017). DOI: 10.1371/journal.pone.0171344
Tatler, A. L. & Jenkins, G. TGF-β activation and lung fibrosis. Proc. Am. Thorac. Soc. 9, 130–136 (2012). DOI: 10.1513/pats.201201-003AW
Inoue, Y. et al. Diagnostic and prognostic biomarkers for chronic fibrosing interstitial lung diseases with a progressive phenotype. Chest 158, 646–659 (2020). DOI: 10.1016/j.chest.2020.03.037
Suzuki, H. et al. Mechanism of neutrophil recruitment induced by IL-8 in chronic sinusitis. J. Allergy Clin. Immunol. 98, 659–670 (1996). DOI: 10.1016/S0091-6749(96)70100-8
Stifano, G. & Christmann, R. B. Macrophage involvement in systemic sclerosis: Do we need more evidence?. Curr. Rheumatol. Rep. 18, 2 (2015). DOI: 10.1007/s11926-015-0554-8
Jacquerie, P. et al. Induced sputum in systemic sclerosis: A new potential for biomarkers in SSc. Eur. Respir. J. 54 (Suppl. 63), (2019).
Jacquerie, P. et al. Inflammatory profile of induced sputum composition in systemic sclerosis: A comparison with healthy volunteers. medRxiv 10.1101/2020.11.23.20236679 (2020). DOI: 10.1101/2020.11.23.20236679
Khalil, N. & Greenberg, A. H. The role of TGF-beta in pulmonary fibrosis. Ciba Found. Symp. 157, 194–207 (1991) (discussion 207–11).
van Caam, A. et al. TGFβ-mediated expression of TGFβ-activating integrins in SSc monocytes: Disturbed activation of latent TGFβ?. Arthritis Res. Ther. 22, 42 (2020). DOI: 10.1186/s13075-020-2130-5
Cossu, M. et al. Earliest phase of systemic sclerosis typified by increased levels of inflammatory proteins in the serum. Arthritis Rheumatol. 69, 2359–2369 (2017). DOI: 10.1002/art.40243
La Montagna, G., D’Angelo, S. & Valentini, G. Cross-sectional evaluation of YKL-40 serum concentrations in patients with systemic sclerosis. Relationship with clinical and serological aspects of disease. J. Rheumatol. 30, 2147–2151 (2003).
Nordenbæk, C. et al. High serum levels of YKL-40 in patients with systemic sclerosis are associated with pulmonary involvement. Scand. J. Rheumatol. 34, 293–297 (2005). DOI: 10.1080/03009740510018598
Schnyder, B., Bogdan, J. A. & Schnyder-Candrian, S. Role of interleukin-8 phosphorylated kinases in stimulating neutrophil migration through fibrin gels. Lab. Investig. J. Tech. Methods Pathol. 79, 1403–1413 (1999).
Feghali, C. A., Bost, K. L., Boulware, D. W. & Levy, L. S. Mechanisms of pathogenesis in scleroderma. I. Overproduction of interleukin 6 by fibroblasts cultured from affected skin sites of patients with scleroderma. J. Rheumatol. 19, 1207–1211 (1992).
Lauretis, A. D. et al. Serum interleukin 6 is predictive of early functional decline and mortality in interstitial lung disease associated with systemic sclerosis. J. Rheumatol. 40, 435–446 (2013). DOI: 10.3899/jrheum.120725
Kania, G., Rudnik, M. & Distler, O. Involvement of the myeloid cell compartment in fibrogenesis and systemic sclerosis. Nat. Rev. Rheumatol. 15, 288–302 (2019). DOI: 10.1038/s41584-019-0212-z
Kim, W.-U. et al. Elevated matrix metalloproteinase-9 in patients with systemic sclerosis. Arthritis Res. Ther. 7, R71 (2005). DOI: 10.1186/ar1454
Distler, O. et al. Nintedanib for systemic sclerosis-associated interstitial lung disease. N. Engl. J. Med. 380, 2518–2528 (2019). DOI: 10.1056/NEJMoa1903076
LeRoy, E. C. et al. Scleroderma (systemic sclerosis): Classification, subsets and pathogenesis. J. Rheumatol. 15, 202–205 (1988).
LeRoy, E. C. & Medsger, T. A. Criteria for the classification of early systemic sclerosis. J. Rheumatol. 28, 1573–1576 (2001).