Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Aug;45(8):1153-1158.
doi: 10.3899/jrheum.170518. Epub 2018 Jul 1.

KL-6 But Not CCL-18 Is a Predictor of Early Progression in Systemic Sclerosis-related Interstitial Lung Disease

Gloria A Salazar  1   2 , Masataka Kuwana  1   2 , Minghua Wu  1   2 , Rosa M Estrada-Y-Martin  1   2 , Jun Ying  1   2 , Julio Charles  1   2 , Maureen D Mayes  1   2 , Shervin Assassi  3   4
Affiliations

KL-6 But Not CCL-18 Is a Predictor of Early Progression in Systemic Sclerosis-related Interstitial Lung Disease

Gloria A Salazar et al. J Rheumatol. 2018 Aug.

Abstract

Objective: The 2 pneumoproteins, KL-6 and CCL-18, are promising biomarkers in systemic sclerosis (SSc)-related interstitial lung disease (ILD). Our goal was to determine their predictive significance for forced vital capacity % (FVC%) decline within the first year of followup in patients with early SSc-ILD.

Methods: Early SSc patients with imaging-verified ILD enrolled in the Genetics versus Environment in Scleroderma Outcome Study (GENISOS) cohort were included. Annualized rate of change in FVC% based on the baseline and followup measurement within 12-18 months was used as the surrogate outcomes for ILD progression.

Results: Eighty-two early SSc-ILD patients with mean disease duration of 2.3 years were investigated. FVC% change ranged from -23% to 38%. Baseline KL-6 levels were higher in patients than healthy controls (p < 0.0001). Higher KL-6 levels were predictive of faster FVC% decline at the 1-year followup (r = -0.23, p = 0.037). Upon categorizing KL-6 using a previously published cutoff of 1273 U/ml, its predictive significance remained in the univariable model (b = -0.07, p = 0.01), indicating that patients with positive KL-6 had on average 7% more decline in annualized percent change of FVC%. Moreover, KL-6 remained an independent predictor after adjustment for sex, disease type, anti-Scl-70, and immunosuppressive treatment status in multivariable models. Although CCL-18 was higher in patients than controls (p < 0.001), its levels did not predict FVC decline rate (p = 0.458).

Conclusion: KL-6 but not CCL-18 is predictive of early SSc-ILD progression. KL-6 is a promising pneumoprotein that can contribute to SSc-ILD clinical trial enrichment.

Keywords: BIOMARKERS; INTERSTITIAL LUNG DISEASE; SYSTEMIC SCLEROSIS.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
A. KL-6 levels (U/ml) in patients with SSc versus controls (dashed line = 1273 cutoff). B. FVC% annualized percent change in KL-6-positive versus -negative patients based on a cutoff of 1273 U/ml. C. CCL-18 levels (ng/ml) in patients with SSc versus controls. D. FVC% annualized percent change in CCL-18-positive versus -negative patients based on a cutoff of 140 ng/ml. Lower values in FVC% percent change correspond to a faster FVC decline. SSc: systemic sclerosis; FVC%: % forced vital capacity.
See this image and copyright information in PMC

References

    1. Steen VD, Medsger TA. Changes in causes of death in systemic sclerosis, 1972–2002. Ann Rheum Dis 2007;66:940–4. - PMC - PubMed
    1. Kuwana M, Shirai Y, Takeuchi T. 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 2016;43:1825–31. - PubMed
    1. Christmann RB, Sampaio-Barros P, Stifano G, Borges CL, de Carvalho CR, Kairalla R, et al. Association of interferon- and transforming growth factor beta-regulated genes and macrophage activation with systemic sclerosis-related progressive lung fibrosis. Arthritis Rheumatol 2014;66:714–25. - PMC - PubMed
    1. Hoffmann-Vold AM, Tennoe AH, Garen T, Midtvedt O, Abraityte A, Aalokken TM, et al. High level of chemokine CCL 18 is associated with pulmonary function deterioration, lung fibrosis progression, and reduced survival in systemic sclerosis. Chest 2016; 150:299–306. - PubMed
    1. Assassi S, Del Junco D, Sutter K, McNearney TA, Reveille JD, Karnavas A, et al. Clinical and genetic factors predictive of mortality in early systemic sclerosis. Arthritis Rheum 2009;61:1403–11. - PMC - PubMed

Publication types