Serum KL-6 levels reflect the severity of interstitial lung disease associated with connective tissue disease

Abstract

Background Biomarkers have been actively investigated to supplement functional and imaging modalities to predict the severity, therapeutic responsiveness, and progression of connective tissue disease-associated interstitial lung disease (CTD-ILD). This study aimed to evaluate Krebs von den Lungen 6 (KL-6) as a potential biomarker reflecting the severity of CTD-ILD as assessed through computed tomography (CT) and pulmonary function test (PFT) parameters. Methods This retrospective study included 549 Korean patients with rheumatoid arthritis, systemic sclerosis, inflammatory myositis, and other CTDs with or without concurrent ILD. Serum KL-6 concentration (U/mL) was measured using the latex-enhanced immunoturbidimetric assay method. CT and PFT results were collected within 1 year of serum collection. A semiquantitative grade of ILD extent was evaluated through CT scan (grade 1, 0–25%; grade 2, 26–50%; grade 3, 51–75%; grade 4, 76–100%). Results CTD-ILD patients ( n = 165) had elevated serum KL-6 levels compared to CTD patients without ILD ( n = 384) ( p < 0.001), and those findings were preserved after adjusting for age, sex, and CTD type. The semiquantitative grade of ILD on CT scan was significantly proportional to the KL-6 level, and the optimal cut-off KL-6 value effectively differentiated each ILD grade. The percent diffusing capacity of the lung for carbon monoxide (DLCO) ( p < 0.001) and forced vital capacity (FVC) ( p < 0.001) parameters had a moderate, negative correlation with the KL-6 level. Conclusion Serum KL-6 levels were increased in CTD-ILD patients and had a positive correlation with CT grade and a negative correlation with FVC and DLCO. Serum KL-6 levels may reflect CTD-ILD severity. Electronic supplementary material The online version of this article (10.1186/s13075-019-1835-9) contains supplementary material, which is available to authorized users.

Comparative Profiling of Serum Protein Biomarkers in Rheumatoid Arthritis–Associated Interstitial Lung Disease and Idiopathic Pulmonary Fibrosis

“…Consistent with this paradigm, a number of studies have demonstrated increased titers of anti-cyclic citrullinated peptide (anti-CCP) antibodies in patients with RA-ILD (9)(10)(11)(12). Apart from high titers of anti-CCP antibodies and rheumatoid factor (RF) (13), several studies have shown associations between RA-ILD and alternative biomarkers (many of which are also associated with idiopathic pulmonary fibrosis [IPF] [14]), such as the epithelial cell-derived Krebs von den Lungen 6 (KL-6) antigen (15), matrix metalloproteinase 7 (MMP-7), pulmonary and activation-regulated chemokine (PARC), surfactant protein D (SP-D), and interferon-γ-inducible protein 10 (IP-10/CXCL10) (16,17).…”

Serum KL‐6 level is a prognostic marker in patients with anti‐MDA5 antibody‐positive dermatomyositis associated with interstitial lung disease

“…Recently, circulating KL‐6 is shown to be a sensitive marker of the activity of various types of ILD . Emerging evidence has demonstrated that KL‐6 levels correlate with high‐resolution computed tomography (HRCT) findings, pulmonary function test (PFT), and some clinical parameters in connective tissue disease (CTD)‐ILDs, thus reflecting the severity of CTD‐ILD . The poor prognosis of PM/DM‐ILD also has a positive correlation with serum KL‐6 levels …”

Fibrosis and Damage Markers in Occupational Interstitial Lung Diseases

“…High levels of KL-6 are seen in the sera of patients with idiopathic interstitial pneumonia, drug-induced ILD, pulmonary sarcoidosis, and connective tissue diseaseassociated ILD. 9,10 It has been reported that KL-6 has a high level of sensitivity and specificity for ILD such as idiopathic pulmonary fibrosis (IPF), and serum levels of KL-6 are 70-100% significantly higher in IPF. Analysis of the relationship between KL-6 serum levels and disease activity suggests that KL-6 serum levels are significantly correlated with the severity of the interstitial pneumonia and IPF.…”