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Circulating Biomarkers and Disease Activity in Systemic Sclerosis-Associated Interstitial Lung Disease

Supparerk Disayabutr¹, Prateep Raksasagulwong¹, Chayawee Muangchan², Phakpoom Thiravit³, Suwimon Wonglaksanapimon³

Affiliation : ¹ Division of Respiratory Disease and Tuberculosis, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; ² Division of Rheumatology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; ³ Department of Radiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand

Background: Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is a major cause of death in SSc patients. Several studies have reported that serum anti-Scl-70, Krebs von Lungren-6 (KL-6), and surfactant protein D (SP-D) levels are associated with the presence and progression of ILD in SSc patients.
Objective: To examine the correlation between levels of these serum biomarkers and disease severity determined by baseline dyspnea index (BDI), high-resolution computed tomography (HRCT) score, and pulmonary function tests.
Materials and Methods: The present study was a single-center, cross-sectional study. Serum anti-Scl-70, KL-6, and SP-D from 20 SSc-ILD patients and five non-ILD subjects were measured. The BDI, HRCT score, and pulmonary function tests were used to assess the severity of ILD in SSc-ILD patients. HRCT abnormalities, including ground-glass opacity (GGO), fibrosis, and honeycombing, were scored by using the semi-quantitative scoring system.
Results: Serum anti-Scl-70, KL-6, and SP-D in SSc-ILD patients were significantly higher than those in non-ILD subjects. There was a moderate correlation between diffusing capacity for carbon monoxide (DLCO) and serum KL-6 levels (r=–0.551, p=0.022), while the pulmonary fibrosis (PF) score exhibited a strong correlation with serum KL-6 levels (r=0.630, p=0.003). The PF score had a moderate negative correlation with forced vital capacity (FVC) (r=–0.515, p=0.034) and a strong negative correlation with total lung capacity (TLC) and DLCO (r=–0.625, p=0.007, and r=–0.762, p<0.001, respectively).
Conclusion: The levels of serum KL-6, and SP-D are elevated in SSc-ILD patients. Serum KL-6 may be a useful non-invasive biomarker for the disease severity, as determined by DLCO and the extent of fibrosis on HRCT, in patients with SSc-ILD.

Trial registration: Thai Clinical Trials Registry, TCTR20200314001, registered 13 March 2020, retrospectively registered at http://www.thaiclinicaltrials.org/show/TCTR20200314001

Received 9 January 2023 | Revised 8 May 2023 | Accepted 19 May 2023
DOI: 10.35755/jmedassocthai.2023.06.13855

Keywords : Scleroderma; Systemic sclerosis; Interstitial pneumonia; Interstitial lung disease; Fibrosis; Biomarker


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