Diagnostic Role of Osteopontin in Interstitial Lung Disease
DOI:
https://doi.org/10.31584/jhsmr.2021780Keywords:
diagnostic marker, interstitial lung disease, osteopontinAbstract
Objective: Early diagnosis of interstitial lung disease (ILD) is desirable not only to better define pathobiological mechanisms, but also to customize treatment protocols. As osteopontin (OPN) expression may be linked to the fibrotic remodelling in ILD, this present study was planned to evaluate the usefulness of its estimation in serum for the diagnosis of ILD.
Material and Methods: Serum OPN levels were estimated by enzyme-linked immunosorbent assay in 52 diagnosed cases of ILD, that were then compared with 46 patients with chronic obstructive lung disease and 46 apparently healthy controls.
Results: Median levels of serum OPN were found to be significantly higher in patients with ILD, 2.186 nanograms per milliliter (ng/ml), as compared to patients with chronic obstructive lung disease and healthy controls (1.687 and 1.923 ng/ml, respectively). The best cutoff levels of OPN, for diagnosis of ILD, was found to be >1.08 ng/ml; with a sensitivity of 88.4% and specificity of 32.6%. Of the various subtypes, serum OPN levels were found to be highest in patients with idiopathic pulmonary fibrosis and interstitial pneumonia with autoimmune features; although the difference in levels between various subgroups was not found to be statistically significant (p-value=0.495).
Conclusion: Serum concentration of OPN was found to be increased in patients with ILD and may be used to aid diagnosis. This opens new avenues for future research in patients with ILD, not only for the validation of the diagnostic abilities of OPN, but also as a potential target in its treatment.
References
Ask K, Hambly N, Kolb MRJ. Biomarkers in interstitial lung disease: moving towards composite indexes and multimarkers? Curr Pulmonol Reports 2015;4:125-9.
Ley B, Brown KK, Collard HR. Molecular biomarkers in idiopathic pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol 2014; 307:681-91.
Kumar A, Prashant A, Gupta KA, Gautam KA, Kumar A, Choudhri A. Profile of interistial lung diseases at tertiary care centre of northern India. Eur J Pharm Med Res 2016;3:368-74.
Hambly N, Shimbori CH, Kolb MA. Molecular classification of idiopathic pulmonary fibrosis: personalized medicine, genetics and biomarkers. Respirology 2015;20:1010–22.
Kahles F, Findeisen HM, Bruemmer D, Osteopontin: A novel regulator at the cross roads of inflammation, obesity and diabetes. Molecular Metabolism 2014;3:384-93.
Kadota J, Mizunoe S, Mito K, Mukae H, Yoshioka S, Kawakami K, High plasma concentrations of osteopontin in patients with interstitial pneumonia. Respir Med 2005;99:111-7.
Sato W, Tomita A, Ichikawa D, Lin Y, Kishida H, Miyake S. CCR2(+) CCR5(+) t cells produce matrix metalloproteinase-9 and osteopontin in the pathogenesis of multiple sclerosis. J Immuno 2012;189:5057-65.
Agnholt J, Kelsen J, Schack L, Hvas CL, Dahlerup JF, Sorensen ES. Osteopontin, a protein with cytokine-like properties, is associated with inflammation in Crohn's disease. Scandinavian J Immuno 2007;65:453-60.
Wong CK, Lit LC, Tam LS, Li EK, Lam CW. Elevation of plasma osteopontin concentration is correlated with disease activity in patients with systemic lupus erythematosus. Rheumatology 2005;44:602-6.
Xu L, Ma X, Wang Y, Li X, Qi Y, Cui B. The expression and pathophysiological role of Osteopontin in Graves' disease. J Clin Endocrinol Metab 2011;96:1866-70.
Raja R, Kale S, Thorat D, Soundararajan G, Lohite K, Mane A. Hypoxia-driven osteopontin contributes to breast tumor growth through modulation of hif 1 alpha-mediated VEGFdependent angiogenesis. Oncogene 2014;33:2053-64.
Tilli TM, Franco VF, Robbs BK, Wanderley JL, Da Silva FR, De Mello KD. Osteopontin-c splicing isoform contributes to ovarian cancer progression. Mol Cancer Res 2011;9:280-93.
Waller AH, Sanchez-Ross M, Kaluski E, Klapholz M. Osteopontin in cardiovascular disease: a potential therapeutic target. Cardiol Rev 2010;18:125-31.
Psarras S, Mavroidis M, Sanoudou D, Davos CH, Xanthou G, Varela AE. Regulation of adverse remodelling by osteopontin in a genetic heart failure model. Eur Heart J 2012;33:1954-96.
Hirose M, Tozawa K, Okada A, Hamamoto S, Higashibata Y, Gao B. Role of osteopontin in early phase of renal crystal formation: immunohistochemical and microstructural comparisons with osteopontin knock-out mice. Urol Res 2012;40:121-9.
Takahashi F, Takahashi K, Okazaki T, Maeda K, Lenaga H, Maeda M. Role of osteopontin in the pathogenesis of bleomycininduced pulmonary fibrosis. Am J Respir Cell Mol Biol 2001;24: 264–71.
Zuo F, Kaminski N, Eugui E, Allard J, Yakhini Z, Ben-Dor A et al. Gene expression analysis reveals matrilysin as a key regulator of pulmonary fibrosis in mice and humans. Proc Natl Acad Sci 2002;99:6292–7.
Cottin V, Hirani NA, Hotchkin DL, Nambiar AM, Ogura T, Otalo M , et al. Presentation, diagnosis and clinical course of the spectrum of progressive fibrosing interstitial lung diseases. Eur Respir Rev 2018;27:180076.
Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for the Diagnosis. Management and Prevention of COPD [monograph on the Internet]. Fontana: GOLD; 2017 [cited 2020 May 25]. Available from: https://goldcopd.org/wp-content /uploads/2017/11/GOLD-2018-v6.0-FINAL-revised- 20-Nov_WMS.pdf
Pardo A, Gibson K, Cisneros J, Richards TJ, Yang Y, Becerril C, et al. Up-regulation and profibrotic role of osteopontin in human idiopathic pulmonary fibrosis. PLoS Med 2005;2:891– 903.
O’Regan A. The role of osteopontin in lung disease. Cytokine Growth Factor Rev 2003;14:479-88.
Mangum JB, Bermudez E, Sar M, Everitt JI. Osteopontin expression in particle-induced lung disease. Exp Lung Res 2004;30:585-98.
Ashizawa N, Graf K, Do YS, Nunohiro T, Giachelli CM, et al. Osteopontin is produced by rat cardiac fibroblasts and mediates A(II)-induced DNA synthesis and collagen gel contraction. J Clin Inves 1996;98:2218-27.
Ma JE, Lee SH, Kim YE, Lim SJ, Lee SJ, Jeong YY, Kim HC, Lee JD, Hwang YS, Cho YJ. Comparison of serum osteopontin levels in patients with stable and chronic obstructive pulmonary disease and exacerbation. Tuberc Respir Dis 2011;71: 195-201.
Papaporfyriou A, Loukides S, Kostikas K, Simoes DC, Papatheodorou G, Konstantellou E et al. Increased levels of osteopontin in sputum supernatant in patients with COPD. Chest 2014;146: 951-8.
Ali AA, Azab NY, El-Mahalawy II, Tayel SI, Khalifa EM. Osteopontin in chronic obstructive pulmonary disease: Smokers and ex-smokers. Egypt J Chest Dis Tuberc 2015;64:63-6.
Hillas G, Loukides S, Kostikas K, Simoes D, Petta V, Konstantellou E, et al. Increased levels of osteopontin in sputum supernatant of smoking asthmatics. Cytokine 2013;61:251-5.
Petta V, Loukides S, Kostikas K, Papaioannou AI, Papatheodorou G, Cholidou K, et al. Serum osteopontin in patients with lung cancer and chronic obstructive pulmonary disease: does the co-existence make the difference?. J Thorac Dis 2018;10:740-8.
Bishop E, Theophilus EH, Fearon IM. In vitro and clinical studies examining the expression of osteopontin in cigarette smoke-exposed endothelial cells and cigarette smokers. BMC Cardiovasc Disord 2012;12. doi: 10.1186/1471-2261-12- 75.
Kumar R, Gupta N, Goel N. Spectrum of interstitial lung disease at a tertiary care centre in India. Pneumonol Alergol Pol 2014; 82:218-26.
Singh S, Bridget FC, Sharma BB, Joshi JM, Talwar D, Katiyar S, et al. Interstitial lung disease in India: results of prospective registry. Am J Resp crit care med 2017;195:801-13.
White ES, Xia M, Murray S, Dyal R, Flaherty CM, Flaherty KR, et al. 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 2016;194:1242-51.
Downloads
Published
How to Cite
Issue
Section
License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.