Stock, CJW;
Hoyles, RK;
Daccord, C;
Kokosi, M;
Visca, D;
De Lauretis, A;
Alfieri, V;
... Renzoni, EA; + view all
(2021)
Serum markers of pulmonary epithelial damage in systemic sclerosis-associated interstitial lung disease and disease progression.
Respirology
, 26
(5)
pp. 461-468.
10.1111/resp.13988.
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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.
| Type: | Article |
|---|---|
| Title: | Serum markers of pulmonary epithelial damage in systemic sclerosis-associated interstitial lung disease and disease progression |
| Location: | Australia |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1111/resp.13988 |
| Publisher version: | http://dx.doi.org/10.1111/resp.13988 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | CYFRA 21-1, Krebs von den Lungen-6, MUC1 allele, biomarker, disease progression, systemic sclerosis-associated interstitial lung disease |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10118088 |
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