Circulating Biomarker Analyses in a Longitudinal Cohort of Patients with IPF

In this study, we asked whether levels of select circulating biomarkers in patients with IPF demonstrated changes in response to treatment over time, and whether treatment with pirfenidone and nintedanib led to differential biomarker expression. Serial plasma samples from 48 IPF patients on usual treatment and 6 healthy volunteers were analyzed to identify differentially expressed blood protein. Hypothesis-driven potential biomarker selection was based on recent literature, internal preclinical data, and the PROLIFIC Consortium (1) proposed biomarkers of pulmonary fibrosis. We compared our findings to public databases to provide insights into relevant signaling pathways in IPF. Of the 26 proteins measured, we found that 11 (SP-D, TIMP1, MMP7, CYFRA21-1, YKL40, CA125, sICAM, IP-10, MDC, CXCL13) were significantly elevated in IPF patients compared to healthy volunteers, but their levels did not significantly change over time. In the IPF samples, seven proteins were elevated in the treatment group compared to the no-treatment group. However, protein profiles were not distinguishable between patients on pirfenidone versus nintedanib. We demonstrated that most proteins differentially detected in our samples were predicted to be secreted from the lung epithelial or interstitial compartments. However, a significant minority of the proteins are not known to be transcriptionally expressed by lung cells, suggesting an ongoing systemic response. Understanding the contributions of the sy...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - Category: Cytology Authors: Source Type: research