Serum markers of pulmonary epithelial damage in systemic sclerosis‐associated interstitial lung disease and disease progression
Carmel Stock, Rachel K. Hoyles, Cécile Daccord, Maria Kokosi, Dina Visca, Angelo De Lauretis, Veronica Alfieri, Vasileios Kouranos, George Margaritopoulos, Peter M. George, Philip L. Molyneaux, Felix Chua, Toby M. Maher, David Abraham, Voon H Ong, Jackie Donovan, Piersante Sestini, Christopher P. Denton, Athol U. Wells, Elisabetta Renzoni
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 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.