Abstract
Interstitial lung disease (ILD) is the main cause of death in systemic sclerosis (SSc). The progression of SSc associated ILD (SSc-ILD) is highly variable, and markers predictive of progressive ILD are needed early in the disease course, to aim treatment towards patients likely to develop irreversible fibrosis. KL-6 is a mucin-like glycoprotein expressed on type II pneumocytes, prominently expressed/solubilised when epithelial cell injury occurs. Serum levels of KL-6 were measured in both a retrospective (n=180) and a prospective (n=118) cohort of SSc patients. Genotyping of rs4072037 in MUC1 was carried out using a TaqMan assay. Statistical analysis was performed using STATA12. In both cohorts, KL-6 was lowest in patients without ILD (median:374 (IQR:226-666) U/ml), and highest in patients with extensive (1371 (446-1245) U/ml), rather than limited ILD (729 (872-2816) U/ml, p= 0.0001), according to our staging system based on CT extent, integrated as necessary by FVC. Serum KL-6 was higher in patients carrying the C allele of rs4072037 in both cohorts (981 (U/ml vs 491U/ml p=0.0001 and 932 (568-1310) U/ml vs 1419 (905-2254) U/ml p=0.0015). In the retrospective cohort, on both univariate and multivariate analyses (adjusting for severity, allele carriage, gender, age, ethnicity, and smoking), serum KL-6 was an independent marker of survival and time to decline in FVC ≥5%, FVC ≥10%, and DLCO ≥15%. The association with decline in DLCO15% was replicated in the prospective cohort. Our results suggest that serum KL-6 may be an effective biomarker for predicting decline in lung function, and mortality, in SSc-ILD. This suggests that epithelial cell damage plays an important role in pathogenesis.
Footnotes
Cite this article as: European Respiratory Journal 2018 52: Suppl. 62, PA3664.
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- Copyright ©the authors 2018