Arthritis Res Ther. 2019;21(1):58.

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

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제1저자 이정석 · 교신저자 송영욱

PMID 30764869 PMC6376648 DOI 10.1186/s13075-019-1835-9 IF 5.4 류마티스내과

소속 (3)

Division of Rheumatology, Department of Internal Medicine, Seoul National University College of Medicine, 101, Daehak-ro, Jongno-gu, Seoul, 03080, South Korea.
Division of Rheumatology, Department of Internal Medicine, Seoul National University Bundang Hospital, Gyeonggi-do, South Korea.
Division of Rheumatology, Department of Internal Medicine, Seoul National University College of Medicine, 101, Daehak-ro, Jongno-gu, Seoul, 03080, South Korea. ysong@snu.ac.kr.

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.

Keywords

Connective tissue diseaseInterstitial lung diseaseKL-6Pulmonary function test

Figures

**Fig. 1** Serum KL-6 level of the study population according to the presence of ILD in each CTD. CTD, connective tissue disease; ILD(+), presence of interstitial lung disease; ILD(−), absence of interstitial lung disease; IM, inflammatory myositis; RA, rheumatoid arthritis; SS, Sjogren’s syndrome; SLE, systemic lupus erythematosus; SSc, systemic sclerosis

**Fig. 2** Serum KL-6 levels of ILD patients according to semiquantitative CT grades. CT, computed tomography; grade 1, 0–25% involvement of ILD on chest CT; grade 2, 26–50%; grade 3, 51–75%; grade 4, 76–100%

**Fig. 3** Scatter plot of semiquantitative CT grades and serum KL-6 levels with cut-off value (689.7 U/mL) to discriminate grades 1–2 from grades 3–4

**Fig. 4** Association between serum KL-6 level and a FVC% or b DLCO% of patients with ILD. DLCO%, diffusing capacity of carbon monoxide % predicted; FVC%, forced vital capacity % predicted; ILD, interstitial lung disease

그림 출처: PubMed Central 공개 논문 (PMC6376648)

Conflict of interest statement

ETHICS APPROVAL AND CONSENT TO PARTICIPATE: This study was performed in compliance with the Declaration of Helsinki and was approved by the Institutional Review Board of Seoul National University Hospital (IRB#:0408-131-010). All patients provided written informed consent. CONSENT FOR PUBLICATION: Not applicable. COMPETING INTERESTS: The authors declare that they have no competing interests. PUBLISHER’S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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