https://doi.org/10.4081/reumatismo.2021.1399
Serum KL-6 as predictive and prognostic marker of interstitial lung disease in childhood connective tissue diseases: a pilot study
Submitted: 27 January 2021
Accepted: 27 June 2021
Published: 22 November 2021
Accepted: 27 June 2021
Abstract Views: 6419
PDF: 887
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
This study was aimed to evaluate serum KL-6 levels to determine if this marker can be used for diagnosing and assessing severity of interstitial lung disease (ILD) in children with connective tissue disorders. In total, 40 patients [18 patients with juvenile systemic lupus erythematosus (JSLE), 10 patients with juvenile idiopathic arthritis (JIA), 8 patients with juvenile mixed connective tissue disease (JMCTD), 3 patients with juvenile systemic sclerosis (JSSc), and 1 patient with juvenile dermatomyositis (JDM)] and 20 healthy controls were included in this study. Age, sex, and duration of CTD and ILD (if any) were recorded. Blood samples from all the patients and controls were examined by ELISA. 20 of the 40 patients with CTD (50%) had ILD, 12 were mild and 8 were severe as assessed by spirometry. The median serum KL-6 level was 102.7 U/mL (76.1-180.8) in the CTD with severe ILD group, 72.2 U/mL (58.4- 100.5) in the CTD with mild ILD group, 56.7 U/mL (35.8-68.5) in the CTD without ILD group, and 52.3 U/mL (32.8-62.4) in the control group. KL-6 levels were significantly higher in the CTD with ILD (p<0.05), at a cutoff of 63.4 U/ml identified by ROC curve, serum KL-6 showed a sensitivity of 95.2% and specificity of 89.7%. KL-6 is a valuable biomarker for diagnostic purposes and to detect severity in ILD in childhood CTD.
Cojocaru M, Cojocaru IM, Silosi I, Vrabie CD. Pulmonary manifestations of systemic autoimmune diseases. Maedica 2011; 6: 224-229.
Quezada A, Ramos S, Garcia M, et al. Lung involvement in rheumatologic diseases in children. ALLER Allergol Immunopathol 2012; 40: 88-91.
DOI: https://doi.org/10.1016/j.aller.2011.02.009
Shahane A. Pulmonary hypertension in rheumatic diseases: epidemiology and pathogenesis. Rheum Int (Berlin). 2013; 33: 1655-1667.
DOI: https://doi.org/10.1007/s00296-012-2659-y
Ahuja J, Arora D, Kanne JP, et al. Imaging of Pulmonary Manifestations of Connective Tissue Diseases. RCL Radiol Clin N Am 2016; 54: 1015-1031.
DOI: https://doi.org/10.1016/j.rcl.2016.05.005
Yun D, Stein SL. Review of the cutaneous manifestations of autoimmune connective tissue diseases in pediatric patients. WJD World J Dermatol. 2015; 4: 80.
DOI: https://doi.org/10.5314/wjd.v4.i2.80
Cidon M, Bansal M, Hartl D. Pulmonary manifestations of rheumatologic diseases. Curr Opin Pediatr. 2017; 29: 311-319.
DOI: https://doi.org/10.1097/MOP.0000000000000496
Solomon JJ, Fischer A. Connective tissue disease-associated interstitial lung disease: a focused review. J Intens Care Med. 2015; 30: 392-400.
DOI: https://doi.org/10.1177/0885066613516579
Saper VE, Chen G, Deutsch GH, et al. Emergent high fatality lung disease in systemic juvenile arthritis. Ann Rheum Dis. 2019; 78: 1722-1731.
DOI: https://doi.org/10.1136/annrheumdis-2019-216040
Schulert GS, Yasin S, Carey B, et al. Systemic juvenile idiopathic arthritis-associated lung disease: characterization and risk factors. Arthritis Rheumatol. 2019; 71: 1943-1954.
DOI: https://doi.org/10.1002/art.41073
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: S138-S144.
Salazar GA, Kuwana M, Wu M, et al. KL-6 But Not CCL-18 is a predictor of early progression in systemic sclerosis-related interstitial lung disease. J Rheumatol. 2018; 45: 1153-1158.
DOI: https://doi.org/10.3899/jrheum.170518
Hu C, Wu C, Yang E, et al. Serum KL-6 is associated with the severity of interstitial lung disease in Chinese patients with polymyositis and dermatomyositis. Clin Rheumatol. 2019; 38: 2181-2187.
DOI: https://doi.org/10.1007/s10067-019-04501-9
Benyamine A, Heim X, Resseguier N, et al. Elevated serum Krebs von den Lungen-6 in systemic sclerosis: a marker of lung fibrosis and severity of the disease. Rheumatol Int. 2018; 38: 813-819.
DOI: https://doi.org/10.1007/s00296-018-3987-3
Hanaoka M, Katsumata Y, Kawasumi H, et al. KL-6 is a long-term disease-activity biomarker for interstitial lung disease associated with polymyositis/dermatomyositis, but is not a short-term disease-activity biomarker. Modern Rheumatol. 2019; 29: 625-632.
DOI: https://doi.org/10.1080/14397595.2018.1553488
Hu Y, Wang LS, Jin YP, et al. Serum Krebs von den Lungen-6 level as a diagnostic biomarker for interstitial lung disease in Chinese patients. Clin Respir J. 2017; 11: 337-345.
DOI: https://doi.org/10.1111/crj.12341
Kilinc AA, Arslan A, Yildiz M, et al. Serum KL-6 level as a biomarker of interstitial lung disease in childhood connective tissue diseases: a pilot study. Rheumatol International 2019 [Epub ahead of print).
DOI: https://doi.org/10.1007/s00296-019-04485-4
Aletaha D, Neogi T, Silman AJ, et al. 2010 Rheumatoid Arthritis Classification Criteria An American College of Rheumatology/European League Against Rheumatism Collaborative Initiative. Arthrit Rheum. 2010; 62: 2569-2581.
DOI: https://doi.org/10.1002/art.27584
Aringer M, Costenbader K, Daikh D, et al. 2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus. Ann Rheum Dis 2019; 78: 1151-1159.
DOI: https://doi.org/10.1136/annrheumdis-2020-218615
Lundberg IE, Tjärnlund A, Bottai M, et al. 2017 European League Against Rheumatism/American College of Rheumatology classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups. Ann Rheum Dis 2017; 76: 1955-1964.
DOI: https://doi.org/10.1136/annrheumdis-2017-212786
Zulian F, Woo P, Athreya BH, et al. The Pediatric Rheumatology European Society/American College of Rheumatology/European League against Rheumatism provisional classification criteria for juvenile systemic sclerosis. ART Arthrit Care & Res. 2007; 57: 203-212.
DOI: https://doi.org/10.1002/art.22551
Tanaka Y, Kuwana M, Fujii T, et al. 2019 Diagnostic criteria for mixed connective tissue disease (MCTD): From the Japan research committee of the ministry of health, labor, and welfare for systemic autoimmune diseases. Modern Rheumatol. 2020:1-5.
DOI: https://doi.org/10.1080/14397595.2019.1709944
Raghu G, Remy-Jardin M, Myers JL, et al. Diagnosis of idiopathic pulmonary fibrosis. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med. 2018; 198: e44-e68.
DOI: https://doi.org/10.1164/rccm.201807-1255ST
Kuo CS, Young LR. Interstitial lung disease in children. Curr Opin Pediatr. 2014; 26: 320-327.
DOI: https://doi.org/10.1097/MOP.0000000000000094
Jiang Z, Tao JH, Zuo T, et al. The correlation between miR-200c and the severity of interstitial lung disease associated with different connective tissue diseases. Scand J Rheumatol. 2017; 46: 122-129.
DOI: https://doi.org/10.3109/03009742.2016.1167950
Lancaster LH. Utility of the six-minute walk test in patients with idiopathic pulmonary fibrosis. Multidiscip Respir Med. 2018; 13: 45.
DOI: https://doi.org/10.4081/mrm.2018.215
Shapiro DE. The interpretation of diagnostic tests. Stat Methods Med Res. 1999; 8: 113-134.
DOI: https://doi.org/10.1191/096228099666928387
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: 429-434.
DOI: https://doi.org/10.1111/j.1365-2796.2006.01704.x
Oguz EO, Kucuksahin O, Turgay M, et al. Association of serum KL-6 levels with interstitial lung disease in patients with connective tissue disease: a cross-sectional study. Clin Rheumatol 2016; 35: 663-666.
DOI: https://doi.org/10.1007/s10067-015-3167-8
Fathi M, Barbasso Helmers S, Lundberg IE. KL-6: a serological biomarker for interstitial lung disease in patients with polymyositis and dermatomyositis KL-6: a serological biomarker for interstitial lung disease. J Intern Med. 2012; 271: 589-597.
DOI: https://doi.org/10.1111/j.1365-2796.2011.02459.x
Xue C, Wu N, Li X, et al. 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: 144.
DOI: https://doi.org/10.1186/s12890-017-0489-0
Kobayashi J, Itoh Y, Kitamura S, Kawai T. [Establishment of reference intervals and cut-off value by an enzyme immunoassay for KL-6 antigen, a new marker for interstitial pneumonia]. Rinsho Byori 1996; 44: 653-658.
Zheng P, Liu X, Huang H, et al. Diagnostic value of KL-6 in idiopathic interstitial pneumonia. J Thorac Dis. 2018; 10: 4724-4732.
DOI: https://doi.org/10.21037/jtd.2018.07.54
Lee J, Lee Y, Ha Y, et al. Serum KL-6 levels reflect the severity of interstitial lung disease associated with connective tissue disease. Arthrit Res Ther. 2019; 21: 1-8.
DOI: https://doi.org/10.1186/s13075-019-1835-9
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: 3-13.
DOI: https://doi.org/10.1016/j.resinv.2012.02.001
Fukaya S, Oshima H, Kato K, et al. KL-6 as a novel marker for activities of interstitial pneumonia in connective tissue diseases. Rheumatol Int. 2000; 19: 223.
DOI: https://doi.org/10.1007/s002960000064
How to Cite
El-Beheidy, R. ., Domouky, A., Zidan, H., & Amer, Y. (2021). Serum KL-6 as predictive and prognostic marker of interstitial lung disease in childhood connective tissue diseases: a pilot study. Reumatismo, 73(3). https://doi.org/10.4081/reumatismo.2021.1399
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