Gloria A Salazar1,2, Masataka Kuwana1,2, Minghua Wu1,2, Rosa M Estrada-Y-Martin1,2, Jun Ying1,2, Julio Charles1,2, Maureen D Mayes1,2, Shervin Assassi3,4. 1. From the Department of Internal Medicine, Division of Rheumatology, The University of Texas Health Science Center at Houston, McGovern Medical School, Houston, Texas, USA; Department of Allergy and Rheumatology, Nippon Medical School, Tokyo, Japan. 2. G.A. Salazar, MD, MS, The University of Texas Health Science Center at Houston, McGovern Medical School; M. Kuwana, MD, PhD, Department of Allergy and Rheumatology, Nippon Medical School; M. Wu, MD, PhD, The University of Texas Health Science Center at Houston, McGovern Medical School; R.M. Estrada-Y-Martin, MD, MS, The University of Texas Health Science Center at Houston, McGovern Medical School; J. Ying, MS, The University of Texas Health Science Center at Houston, McGovern Medical School; J. Charles, MS, The University of Texas Health Science Center at Houston, McGovern Medical School; M.D. Mayes, MD, MPH, The University of Texas Health Science Center at Houston, McGovern Medical School; S. Assassi, MD, MS, The University of Texas Health Science Center at Houston, McGovern Medical School. 3. From the Department of Internal Medicine, Division of Rheumatology, The University of Texas Health Science Center at Houston, McGovern Medical School, Houston, Texas, USA; Department of Allergy and Rheumatology, Nippon Medical School, Tokyo, Japan. shervin.assassi@uth.tmc.edu. 4. G.A. Salazar, MD, MS, The University of Texas Health Science Center at Houston, McGovern Medical School; M. Kuwana, MD, PhD, Department of Allergy and Rheumatology, Nippon Medical School; M. Wu, MD, PhD, The University of Texas Health Science Center at Houston, McGovern Medical School; R.M. Estrada-Y-Martin, MD, MS, The University of Texas Health Science Center at Houston, McGovern Medical School; J. Ying, MS, The University of Texas Health Science Center at Houston, McGovern Medical School; J. Charles, MS, The University of Texas Health Science Center at Houston, McGovern Medical School; M.D. Mayes, MD, MPH, The University of Texas Health Science Center at Houston, McGovern Medical School; S. Assassi, MD, MS, The University of Texas Health Science Center at Houston, McGovern Medical School. shervin.assassi@uth.tmc.edu.
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.
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.
Authors: Elizabeth R Volkmann; Donald P Tashkin; Masataka Kuwana; Ning Li; Michael D Roth; Julio Charles; Faye N Hant; Galina S Bogatkevich; Tanjina Akter; Grace Kim; Jonathan Goldin; Dinesh Khanna; Philip J Clements; Daniel E Furst; Robert M Elashoff; Richard M Silver; Shervin Assassi Journal: Arthritis Rheumatol Date: 2019-11-01 Impact factor: 10.995
Authors: Shervin Assassi; Ning Li; Elizabeth R Volkmann; Maureen D Mayes; Dennis Rünger; Jun Ying; Michael D Roth; Monique Hinchcliff; Dinesh Khanna; Tracy Frech; Philip J Clements; Daniel E Furst; Jonathan Goldin; Elana J Bernstein; Flavia V Castelino; Robyn T Domsic; Jessica K Gordon; Faye N Hant; Ami A Shah; Victoria K Shanmugam; Virginia D Steen; Robert M Elashoff; Donald P Tashkin Journal: Arthritis Rheumatol Date: 2021-04-20 Impact factor: 15.483
Authors: Dinesh Khanna; Alain Lescoat; David Roofeh; Elana J Bernstein; Ella A Kazerooni; Michael D Roth; Fernando Martinez; Kevin R Flaherty; Christopher P Denton Journal: Arthritis Rheumatol Date: 2021-11-10 Impact factor: 15.483