Significance of serum Krebs von den Lungen-6 in systemic sclerosis

Egyptian Rheumatology and Rehabilitation - Tập 50 - Trang 1-9 - 2023
Noha Hosni Ibrahim1, Yasser Abd-Elaziz Abd-Elhamid1, Refaat Mostafa El Tanawy1, Rasha Abdel Hameed1, Hanaa Alaa Mahmoud Elbastawesy1
1Benha Faculty of Medicine, Banha, Egypt

Tóm tắt

Systemic sclerosis (SSc) is a well-known multi-system connective tissue disease, it has an unidentified aetiology that is characterised by abnormal immune system activation, vascular injury, which may progress to faulty neovascularization and inadequate vessel remodelling, and tissue scarring of the skin, lungs, and other internal viscera. Krebs von den Lungen-6 is a kind of transmembrane glycoprotein of type II alveolar epithelial cells and is specific for determining its damage. Regardless of the cause, serum Krebs von den Lungen-6 levels have been investigated in interstitial lung disease (ILD) of several etiologies and have been found to be a significant serum marker for ILD. The current research aims to look into the relationship between serum Krebs von den Lungen-6 levels and disease severity and clinical manifestations, specifically interstitial pulmonary fibrosis, in patients with SSc. In this study, 30 patients with systemic sclerosis and 30 control subjects—15 dermatomyositis patients and 15 healthy volunteers— were also incorporated to see if the change in serum Krebs von den Lungen-6 levels is specific for SSc as dermatomyositis is another connective tissue disorder with lung affection. A statistically significant difference (P < 0.001) in the median value of Krebs von den Lungen-6 when compared to the control groups was observed, which was 447.95 (145.68–817.98) in the SSc patients group, 158.80 (130.00–730.70) in the dermatomyositis group, and 48.10 (39.50–103.90) in the healthy control group. A significantly higher median value of Krebs von den Lungen-6 in ground glass, honeycombing, and nodular HRCT was established, with P-value (P < 0.001). There was a highly statistically significant discrepancy in the median Krebs von den Lungen-6 value between patients with ILD (717.7) and patients without ILD (145.7) with P-value (P < 0.001). A statistically significant positive correlation was found between Krebs von den Lungen-6 (U/ml) and Disease duration (years), Medsger severity scale, Digital ulceration, modified Rodnan skin score (MRSS), and P-value (P < 0.05). Krebs von den Lungen-6 could be a scleroderma biomarker. It has been linked to the development and severity of interstitial lung disease in systemic sclerosis patients and may shed light on the pathophysiology of some fibrotic lung changes.

Tài liệu tham khảo

Denton CP, Khanna D (2017) Systemic sclerosis. Lancet 390(10103):1685–1699. https://doi.org/10.1016/S0140-6736(17)30933-9 Furue M, Mitoma C, Mitoma H et al (2017) Pathogenesis of systemic sclerosis–current concept and emerging treatments. Immunol Res 65:790–797 Tyndall AJ, Bannert B, Vonk M et al (2010) Causes and risk factors for death in systemic sclerosis: a study from the EULAR Scleroderma Trials and Research (EUSTAR) database. Ann Rheum Dis 69(10):1809–1815 Steen VD, Medsger TA (2007) Changes in causes of death in systemic sclerosis, 1972–2002. Ann Rheum Dis 66:940–944 Nihtyanova SI, Schreiber BE, Ong VH et al (2014) Prediction of pulmonary complications and long-term survival in systemic sclerosis. Arthritis Rheum 66:1625–1635 Distler O, Highland KB, Gahlemann M et al (2019) Nintedanib for systemic sclerosis–associated interstitial lung disease. N Engl J Med 380:2518–2528 Behr J, Prasse A, Kreuter M et al (2021) Pirfenidone in patients with progressive fibrotic interstitial lung diseases other than idiopathic pulmonary fibrosis (RELIEF): a double-blind, randomised, placebo-controlled, phase 2b trial. Lancet Respir Med 9:476–486 Hoffmann-Vold AM, Maher TM, Philpot EE et al (2020) The identification and management of interstitial lung disease in systemic sclerosis: evidence-based European consensus statements. Lancet Rheumatol 2:e71–e83 Kuwana M, Shirai Y, Takeuchi T (2016) Elevated serum Krebs von den Lungen-6 in early disease predicts subsequent deterioration of pulmonary function in patients with systemic sclerosis and interstitial lung disease. J Rheumatol 43:1825–1831 Van den Hoogen F, Khanna D, Fransen J, Johnson SR, Baron M, Tyndall A et al (2013) 2013 Classification criteria for systemic sclerosis: an American college of rheumatology/European league against rheumatism collaborative initiative. Ann Rheum Dis 72(11):1747–1755. https://doi.org/10.1136/annrheumdis-2013-204424 Lundberg IE, Tjärnlund A, Bottai M, Werth VP, Pilkington C, Visser M et al (2017) 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 76(12):1955–1964 Khanna D, Furst DE, Clements PJ, Allanore Y, Baron M, Czirjak L et al (2017) Standardization of the modified Rodnan skin score for use in clinical trials of systemic sclerosis. J Scleroderma Relat Disord 2(1):11–18 Medsger TA Jr, Bombardieri S, Czirjak L, Scorza R, Della Rossa A, Bencivelli W (2003) Assessment of disease severity and prognosis. Clin Exp Rheumatol 21(3 Suppl 29):S42–S46 Benyamine A, Heim X, Resseguier N, Bertin D, Gomez C, Ebbo M, Harlé JR, Kaplanski G, Rossi P, Bardin N, Granel B (2018) Elevated serum Krebs von den Lungen-6 in systemic sclerosis: a marker of lung fibrosis and severity of the disease. Rheumatol Int 38(5):813–819. https://doi.org/10.1007/s00296-018-3987-3 Chen F, Lu X, Shu X, Peng Q, Tian X, Wang G (2015) Predictive value of serum markers for the development of interstitial lung disease in patients with polymyositis and dermatomyositis: a comparative and prospective study. Intern Med J 45(6):641–647. https://doi.org/10.1111/imj.12754 Takanashi S, Nishina N, Nakazawa M, Kaneko Y, Takeuchi T (2019) Usefulness of serum Krebs von den Lungen-6 for the management of myositis-associated interstitial lung disease. Rheumatology 58:1034–1039. https://doi.org/10.1093/rheumatology/key420 Volkmann ER, Tashkin DP, Kuwana M, Li N, Roth MD, Charles J, Hant FN, Bogatkevich GS, Akter T, Kim G et al (2019) Progression of interstitial lung disease in systemic sclerosis: the importance of pneumoproteins Krebs von den Lungen 6 and CCL18. Arthritis Rheumatol 71:2059–2067. https://doi.org/10.1002/art.41020 Cao XY, Hu SS, Xu D, Li MT, Wang Q, Hou Y, Zeng XF (2019) Serum levels of Krebs von den Lungen-6 as a promising marker for predicting occurrence and deterioration of systemic sclerosis-associated interstitial lung disease from a Chinese cohort. Int J Rheum Dis 22(1):108–115. https://doi.org/10.1111/1756-185X.13452 Bonella F, Volpe A, Caramaschi P et al (2011) Surfactant protein D and KL-6 serum levels in systemic sclerosis: correlation with lung and systemic involvement. Sarcoidosis Vasc Diffuse Lung Dis 28(1):27–33 Salazar GA, Kuwana M, Wu M, Estrada-Y-Martin RM, Ying J, Charles J, Mayes MD, Assassi S (2018) KL-6 but not CCL-18 is a predictor of early progression in systemic sclerosis-related interstitial lung disease. J Rheumatol 45:1153–1158. https://doi.org/10.3899/jrheum.170518 Shirai Y, Fukue R, Kaneko Y, Kuwana M (2021) Clinical relevance of the serial measurement of Krebs von den Lungen-6 levels in patients with systemic sclerosis-associated interstitial lung disease. Diagnostics 11(11):2007. https://doi.org/10.3390/diagnostics11112007 Wang Y, Chen S, Lin J, Xie X, Hu S, Lin Q, Zheng K, Du G, Huang X, Zhang G, Gargani L, Matucci-Cerinic M, Furst DE (2020) Lung ultrasound B-lines and serum KL-6 correlate with the severity of idiopathic inflammatory myositis-associated interstitial lung disease. Rheumatology 59(8):2024–2029. https://doi.org/10.1093/rheumatology/kez571 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 Zhang T, Shen P, Duan C, Gao L. KL-6 as an Immunological Biomarker Predicts the Severity, Progression, Acute Exacerbation, and Poor Outcomes of Interstitial Lung Disease: A Systematic Review and Meta-Analysis. Front Immunol. 2021;12:745233. https://doi.org/10.3389/fimmu.2021.745233. Isoda K, Kotani T, Takeuchi T, Konma J, Ishida T, Hata K et al (2018) Potential of Krebs von den Lungen-6 as a predictor of relapse in interstitial pneumonia with anti-aminoacyl tRNA synthetase antibodies-positive dermatomyositis. Clin Respir J 12(7):2235–2241. https://doi.org/10.1111/crj.12797