Carbohydrate antigen 15.3 as a serum biomarker of interstitial lung disease in systemic sclerosis patients

Abstract

Background: To determine the usefulness of Ca 15.3 as a candidate biomarker in systemic sclerosis (SSc) patients with interstitial lung disease (ILD).

Methods: Two-hundred-twenty-one SSc patients with Ca 15.3 determinations were considered; 168 had evidence of interstitial lung involvement on high-resolution computed tomography (HRCT); digitalized scans were available for scoring in 84 subjects. Discrimination between patients with or without ILD, was assessed by receiving operating characteristics (ROC) analysis; correlations between HRCT scores and Ca 15.3 were performed. Survival and serial pulmonary function tasting (PFT) data were used for prognostication.

Results: Ca 15.3 serum levels strongly correlated with HRCT scores (r=0.734, p<0.0001) which were predictors of survival at the 20% threshold (p=3.1∗10(-4)). Ca 15.3 had an area under ROC to detect the meaningful 20% fibrosis extent equal to 0.927 and abnormal Ca 15.3 values were capable of differentiating between patients at hi- or low-risk for progression in the group with undetermined disease extent (HR=3.209, confidence interval [CI95]=1.56-6.602, p=0.002). Ca 15.3 outperformed other PFT measures in providing a separation of survival estimates where HRCT scans are unavailable. The combined use of HRCT scores and Ca 15.3 in SSc-ILD patients was more discriminatory (HR=4.824, CI95=2.612-8.912, p<0.0001) than the staging system based on HRCT scores plus FVC (HR=2.657, CI95=1.703-4.147, p<0.0001) and characterized by lower prediction errors (0.2134 vs 0.2234).

Conclusion: Ca 15.3 is a rapid and inexpensive candidate biomarker for SSc-ILD being proportional to the extent of lung injury and specific and sensitive in assessing meaningful extents of the disease with prognostic significance.

Keywords: Biomarker; Carbohydrate antigen 15.3; Interstitial lung disease; Survival; Systemic sclerosis.