Email the author Krebs von den Lungen-6 (KL-6) and Surfactant-D as Biomarkers of Interstitial Lung Disease: A Literature Review
Abstract
Interstitial Lung Disease (ILD) is a group of lung diseases characterized by various patterns of lung tissue damage, including inflammation and fibrosis of the lung interstitium, both with known or unknown causes (idiopathic). In establishing the diagnosis of ILD, a comprehensive approach including history-taking, physical examination, and supporting examinations, is needed and managed in a multidisciplinary manner. Biomarkers are diagnostic tools known to be accessible, inexpensive, reproducible, and non-invasive for helping diagnose ILD patients. Growing evidence has supported the idea that many biomarker molecules can detect lung injury in ILD, including Krebs von de lungen-6 (KL-6) and Surfactant D (SP-D). KL-6 and SP-D could be utilized in the detection, disease monitoring, prognostication, and therapeutic responses of ILD patients. This review aimed to discuss several potential Kl-6 and SP-D biomarkers against ILD and discusses their clinical utility.
Keywords
Full Text:
PDFReferences
Rivera-Ortega P, Molina-Molina M. Interstitial lung diseases in developing countries. Ann Glob Health. 2019;85(1):4.
Travis WD, Costabel U, Hansell DM, King TE, Lynch DA, Nicholson AG, 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, Remy-Jardin M, Richeldi L, Thomson CC, Antoniou KM, Bissell BD, et al. Idiopathic pulmonary fibrosis (an update) and progressive pulmonary fibrosis in adults: An official ATS/ERS/JRS/ALAT clinical practice guideline. Am J Respir Crit Care Med. 2022;205(9):E18–47.
Odackal J, Yu V, Gomez-Manjerres D, Field JJ, Burdick MD, Mehrad B. Circulating fibrocytes as prognostic biomarkers of autoimmune interstitial lung disease. ERJ Open Res. 2020;6(4):00481–2020.
Jee AS, Sahhar J, Youssef P, Bleasel J, Adelstein S, Nguyen M, et al. Review: Serum biomarkers in idiopathic pulmonary fibrosis and systemic sclerosis associated interstitial lung disease - frontiers and horizons. Pharmacol Ther. 2019;202:40–52.
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.
Nishikiori H, Chiba H, Ariki S, Kuronuma K, Otsuka M, Shiratori M, et al. Distinct compartmentalization of SP-A and SP-D in the vasculature and lungs of patients with idiopathic pulmonary fibrosis. BMC Pulm Med. 2014;14:196.
Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK, 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.
Drakopanagiotakis F, Wujak L, Wygrecka M, Markart P. Biomarkers in idiopathic pulmonary fibrosis. Matrix Biol. 2018;68–69:404–21.
Bonella F, Ohshimo S, Boerner E, Guzman J, Wessendorf TE, Costabel U. Serum KL-6 levels correlate with response to pirfenidone in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2015;191:A4398.
Maher TM, Stowasser S, Nishioka Y, White ES, Cottin V, Noth I, et al. Investigating the effects of nintedanib on biomarkers of extracellular matrix turnover in patients with IPF: Design of the randomised placebo-controlled INMARK®trial. BMJ Open Respir Res. 2018;5(1):e000325.
Nakamura M, Okamoto M, Fujimoto K, Ebata T, Tominaga M, Nouno T, et al. A retrospective study of the tolerability of nintedanib for severe idiopathic pulmonary fibrosis in the real world. Ann Transl Med. 2019;7(12):262–262.
Yokoyama A, Kondo K, Nakajima M, Matsushima T, Takahashi T, Nishimura M, et al. Prognostic value of circulating KL-6 in idiopathic pulmonary fibrosis. Respirology. 2006;11(2):164–8.
Ishii H, Kushima H, Kinoshita Y, Fujita M, Watanabe K. The serum KL-6 levels in untreated idiopathic pulmonary fibrosis can naturally decline in association with disease progression. Clin Respir J. 2018;12(9):2411–8.
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.
Bergantini L, Bargagli E, Cameli P, Cekorja B, Lanzarone N, Pianigiani L, et al. Serial KL-6 analysis in patients with idiopathic pulmonary fibrosis treated with nintedanib. Respir Investig. 2019;57(3):290–1.
Okuda R, Hagiwara E, Baba T, Kitamura H, Kato T, Ogura T. Safety and efficacy of pirfenidone in idiopathic pulmonary fibrosis in clinical practice. Respir Med. 2013;107(9):1431–7.
Koga Y, Hachisu Y, Tsurumaki H, Yatomi M, Kaira K, Ohta S, et al. Pirfenidone improves familial idiopathic pulmonary fibrosis without affecting serum periostin levels. Medicina (B Aires). 2019;55(5):161.
Ohshimo S, Ishikawa N, Horimasu Y, Hattori N, Hirohashi N, Tanigawa K, et al. Baseline KL-6 predicts increased risk for acute exacerbation of idiopathic pulmonary fibrosis. Respir Med. 2014;108(7):1031–9.
Matsuzawa Y, Kawashima T, Kuwabara R, Hayakawa S, Irie T, Yoshida T, et al. Change in serum marker of oxidative stress in the progression of idiopathic pulmonary fibrosis. Pulm Pharmacol Ther. 2015;32:1–6.
Maher TM, Oballa E, Simpson JK, Porte J, Habgood A, Fahy WA, et al. An epithelial biomarker signature for idiopathic pulmonary fibrosis: An analysis from the multicentre PROFILE cohort study. Lancet Respir Med. 2017;5(12):946–55.
Majewski S, Szewczyk K, Żal A, Białas AJ, Miłkowska-Dymanowska J, Piotrowski WJ. Serial measurements of circulating KL-6, SP-D, MMP-7, CA19-9, CA-125, CCL18, and periostin in patients with idiopathic pulmonary fibrosis receiving antifibrotic therapy: An exploratory study. J Clin Med. 2021;10(17):3864.
Wang K, Ju Q, Cao J, Tang W, Zhang J. Impact of serum SP-A and SP-D levels on comparison and prognosis of idiopathic pulmonary fibrosis: A systematic review and meta-analysis. Medicine. 2017;96(23):e7083.
Ikeda K, Chiba H, Nishikiori H, Azuma A, Kondoh Y, Ogura T, et al. Serum surfactant protein D as a predictive biomarker for the efficacy of pirfenidone in patients with idiopathic pulmonary fibrosis: A post-hoc analysis of the phase 3 trial in Japan. Respir Res. 2020;21(1):316.
Qi XM, Luo Y, Song MY, Liu Y, Shu T, Liu Y, et al. Pneumoconiosis: Current status and future prospects. Chin Med J (Engl). 2021;134(8):898–907.
Xue C, Wu N, Li X, Qiu M, Du X, Ye Q. Serum concentrations of Krebs von den Lungen-6, surfactant protein D, and matrix metalloproteinase-2 as diagnostic biomarkers in patients with asbestosis and silicosis: A case-control study. BMC Pulm Med. 2017;17(1):144.
Liu J, Zhang R, Song H, Xia Q, Zhao T tong, Pan L, et al. [The effects of long-term exposure to silica dust on serum CC16 and KL-6 levels]. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2019;37(8):567–70.
Andarini SL, Yusrika A, Pamungkasningsih SW, Taufikulhakim FH, Hudoyo A, Nalapraya WY, et al. The surfactant protein D (SP-D) serum levels in Limestone Mining Worker. Jurnal Respirologi Indonesia. 2022;42(2):151–5.
Jalil N, Andarini SL, Ilyas M, Taufik FF. Surfactant protein D level in cement workers. Jurnal Respirologi Indonesia. 2022;42(3):218–25.
Zhou Y, Wang H, Xing J, Liu Y, Cui X, Guo J, et al. Expression levels of surfactant-associated proteins and inflammation cytokines in serum and bronchoalveolar lavage fluid among coal miners: A case-control study. J Occup Environ Med. 2014;56(5):484–8.
Baughman RP, Lower EE, Gibson K. Pulmonary manifestations of sarcoidosis. Presse Med. 2012;41(6 Pt 2):e289-302.
Costabel U, Bonella F, Ohshimo S, Guzman J. Diagnostic modalities in sarcoidosis: BAL, EBUS, and PET. Semin Respir Crit Care Med. 2010;31(4):404–8.
Janssen R, Sato H, Grutters JC, Bernard A, Van Velzen-Blad H, Du Bois RM, 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.
d’Alessandro M, Carleo A, Cameli P, Bergantini L, Perrone A, Vietri L, et al. BAL biomarkers’ panel for differential diagnosis of interstitial lung diseases. Clin Exp Med. 2020;20(2):207–16.
Beketov VD, Lebedeva M V., Mukhin NA, Serova AG, Ponomarev AB, Popova EN, et al. Clinical significance of the determination of surfactant proteins A and D in assessing the activity of lung sarcoidosis. Ter Arkh. 2018;90(3):42–6.
Nukui Y, Yamana T, Masuo M, Tateishi T, Kishino M, Tateishi U, et al. Serum CXCL9 and CCL17 as biomarkers of declining pulmonary function in chronic bird-related hypersensitivity pneumonitis. PLoS One. 2019;14(8):e0220462.
Okamoto T, Fujii M, Furusawa H, Tsuchiya K, Miyazaki Y, Inase N. The usefulness of KL-6 and SP-D for the diagnosis and management of chronic hypersensitivity pneumonitis. Respir Med. 2015;109(12):1576–81.
Takahashi T, Munakata M, Ohtsuka Y, Satoh-Kamachi A, Sato R, Homma Y, et al. Serum KL-6 concentrations in dairy farmers. Chest. 2000;118(2):445–50.
Janssen R, Grutters Jan C, Sato H, van Velzen-Blad H, Zanen P, Kohno N, et al. Analysis of KL-6 and SP-D as disease markers in bird fancier’s lung. Sarcoidosis, Vasculitis, and Diffuse Lung Disease: Official Journal of WASOG. 2005;22(1):51–7.
Onishi Y, Kawamura T, Higashino T, Kagami R, Hirata N, Miyake K. Clinical features of chronic summer-type hypersensitivity pneumonitis and proposition of diagnostic criteria. Respir Investig. 2020;58(1):59–67.
Inase N, Ohtani Y, Usui Y, Miyazaki Y, Takemura T, Yoshizawa Y. Chronic summer-type hypersensitivity pneumonitis: Clinical similarities to idiopathic pulmonary fibrosis. Sarcoidosis, Vasculitis, and Diffuse Lung Disease: Official Journal of WASOG. 2007;24(2):141–7.
Kucejko W, Chyczewska E, Naumnik W, Ossolińska 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.
Antoniou KM, Margaritopoulos G, Economidou F, Siafakas NM. Pivotal clinical dilemmas in collagen vascular diseases associated with interstitial lung involvement. Eur Respir J. 2009;33(4):882–96.
Nakajima H, Harigai M, Hara M, Hakoda M, Tokuda H, Sakai F, et al. KL-6 as a novel serum marker for interstitial pneumonia associated with collagen diseases. J Rheumatol. 2000;27(5):1164–70.
Oyama T, Kohno N, Yokoyama A, Hirasawa Y, Hiwada K, Oyama H, et al. Detection of interstitial pneumonitis in patients with rheumatoid arthritis by measuring circulating levels of KL-6, a human MUC1 mucin. Lung. 1997;175(6):379–85.
Kubo M, Ihn H, Yamane K, Kikuchi K, Yazawa N, Soma Y, et al. Serum KL-6 in adult patients with polymyositis and dermatomyositis. Rheumatology (Oxford). 2000;39(6):632–6.
Kodera M, Hasegawa M, Komura K, Yanaba K, Takehara K, Sato S. 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.
Elhaj M, Charles J, Pedroza C, Liu X, Zhou X, Estrada-Y-Martin RM, 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.
Utsunomiya A, Oyama N, Hasegawa M. Potential biomarkers in systemic sclerosis: A literature review and update. J Clin Med. 2020;9(11):1–25.
Asano Y, Ihn H, Yamane K, Yazawa N, Kubo M, Fujimoto M, 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.
Kaieda S, Gono T, Masui K, Nishina N, Sato S, Kuwana M, et al. Evaluation of usefulness in surfactant protein D as a predictor of mortality in myositis-associated interstitial lung disease. PLoS One. 2020;15(6):e0234523.
Zhong D, Wu C, Bai J, Hu C, Xu D, Wang Q, et al. Comparative diagnostic efficacy of serum Krebs von den Lungen-6 and surfactant D for connective tissue disease-associated interstitial lung diseases: A meta-analysis. Medicine. 2020;99(16):E19695.
DOI: https://doi.org/10.36497/jri.v43i4.439
Refbacks
- There are currently no refbacks.
Copyright (c) 2024 Fanny Fachrucha, Muhamad Rizqy Fadhillah, Syazatul Syakirin Sirol Aflah
INDEXING & PARTNER
| Jurnal Respirologi Indonesia pISSN: 0853-7704 - eISSN: 2620-3162 Address: Jalan Cipinang Bunder No. 19, Cipinang, Pulogadung, Jakarta Timur, DKI Jakarta 13240, Indonesia Phone: +62-21-2247-4845 Email: editor@jurnalrespirologi.org |  An official publication by the Indonesian Society of Respirology (ISR) |
 Creative Commons Attribution-ShareAlike 4.0 International License Statcounter |