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Serum markers of pulmonary epithelial damage in systemic sclerosis-associated interstitial lung disease and disease progression

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Title: Serum markers of pulmonary epithelial damage in systemic sclerosis-associated interstitial lung disease and disease progression
Authors: Stock, CJW
Hoyles, RK
Daccord, C
Kokosi, M
Visca, D
De Lauretis, A
Alfieri, V
Kouranos, V
Margaritopoulos, G
George, PM
Molyneaux, PL
Chua, F
Maher, TM
Abraham, DJ
Ong, V
Donovan, J
Sestini, P
Denton, CP
Wells, AU
Renzoni, EA
Item Type: Journal Article
Abstract: Background and objective The course of systemic sclerosis‐associated interstitial lung disease (SSc‐ILD) is highly variable, and accurate prognostic markers are needed. KL‐6 is a mucin‐like glycoprotein (MUC1) expressed by type II pneumocytes, while CYFRA 21‐1 is expressed by alveolar and bronchiolar epithelial cells. Both are released into the blood from cell injury. Methods Serum KL‐6 and CYFRA 21‐1 levels were measured in a retrospective (n = 189) and a prospective (n = 118) cohort of SSc patients. Genotyping of MUC1 rs4072037 was performed. Linear mixed‐effect models were used to evaluate the relationship with change in lung function parameters over time, while association with survival was evaluated with Cox proportional hazard analysis. Results In both cohorts, KL‐6 and CYFRA 21‐1 were highest in patients with lung involvement, and in patients with extensive rather than limited ILD. KL‐6 was higher in patients carrying the MUC1 rs4072037 G allele in both cohorts. In patients with SSc‐ILD, serum KL‐6, but not CYFRA 21‐1, was significantly associated with DLCO decline in both cohorts (P = 0.001 and P = 0.004, respectively), and with FVC decline in the retrospective cohort (P = 0.005), but not the prospective cohort. When combining the cohorts and subgrouping by severity (median CPI = 45.97), KL‐6 remained predictive of decline in DLCO in both milder (P = 0.007) and more severe disease (P = 0.02) on multivariable analysis correcting for age, gender, ethnicity, smoking history and MUC1 allele carriage. Conclusion Our results suggest serum KL‐6 predicts decline in lung function in SSc, suggesting its clinical utility in risk stratification for progressive SSc‐ILD.
Issue Date: May-2021
Date of Acceptance: 24-Nov-2020
URI: http://hdl.handle.net/10044/1/86143
DOI: 10.1111/resp.13988
ISSN: 1323-7799
Publisher: Wiley
Start Page: 461
End Page: 468
Journal / Book Title: Respirology
Volume: 26
Issue: 5
Copyright Statement: © 2020 The Authors. Respirology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Respirology This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Sponsor/Funder: Action for Pulmonary Fibrosis
Funder's Grant Number: n/a
Keywords: Science & Technology
Life Sciences & Biomedicine
Respiratory System
biomarker
CYFRA 21‐
1
disease progression
Krebs von den Lungen‐
6
MUC1 allele
systemic sclerosis‐
associated interstitial lung disease
SURFACTANT PROTEIN-D
VON DEN LUNGEN-6
HUMAN MUC1 MUCIN
KL-6 LEVELS
FIBROSIS
DETERIORATION
INVOLVEMENT
CLEARANCE
SEVERITY
PREDICTS
CYFRA 21-1
Krebs von den Lungen-6
MUC1 allele
biomarker
disease progression
systemic sclerosis-associated interstitial lung disease
Science & Technology
Life Sciences & Biomedicine
Respiratory System
biomarker
CYFRA 21‐
1
disease progression
Krebs von den Lungen‐
6
MUC1 allele
systemic sclerosis‐
associated interstitial lung disease
SURFACTANT PROTEIN-D
VON DEN LUNGEN-6
HUMAN MUC1 MUCIN
KL-6 LEVELS
FIBROSIS
DETERIORATION
INVOLVEMENT
CLEARANCE
SEVERITY
PREDICTS
Respiratory System
11 Medical and Health Sciences
Publication Status: Published
Online Publication Date: 2020-12-17
Appears in Collections:National Heart and Lung Institute
Faculty of Medicine



This item is licensed under a Creative Commons License Creative Commons