The peripheral blood proteome signature of idiopathic pulmonary fibrosis is distinct from normal and is associated with novel immunological processes

Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial pneumonia. The disease pathophysiology is poorly understood and the etiology remains unclear. Recent advances have generated new therapies and improved knowledge of the natural history of IPF. These gains have been brokered by advances in technology and improved insight into the role of various genes in mediating disease, but gene expression and protein levels do not always correlate. Thus, in this paper we apply a novel large scale high throughput aptamer approach to identify more than 1100 proteins in the peripheral blood of well-characterized IPF patients and normal volunteers. We use systems biology approaches to identify a unique IPF proteome signature and give insight into biological processes driving IPF. We found IPF plasma to be altered and enriched for proteins involved in defense response, wound healing and protein phosphorylation when compared to normal human plasma. Analysis also revealed a minimal protein signature that differentiated IPF patients from normal controls, which may allow for accurate diagnosis of IPF based on easily-accessible peripheral blood. This report introduces large scale unbiased protein discovery analysis to IPF and describes distinct biological processes that further inform disease biology.

Proteomics: Clinical and research applications in respiratory diseases

“…IPF aetiology and pathogenesis are poorly understood . The disease results in aberrant accumulation of extracellular matrix within the interstitium of the lung, promoting impaired gas exchange and respiratory failure …”

“…31 SOMAmers have been used to develop biomarker tools in several forms of respiratory disease including lung cancer, [32][33][34] pulmonary tuberculosis 35,36 and idiopathic pulmonary fibrosis (IPF). 37,38…”

“…63 The disease results in aberrant accumulation of extracellular matrix within the interstitium of the lung, promoting impaired gas exchange and respiratory failure. 37 However, recent studies have started to explore differences in protein expression and profiling in IPF patients. Comparative proteomic analysis of lung tissue samples derived from IPF patients and human donor transplant lungs using 2D gel electrophoresis and matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF)-MS demonstrated significant differences in protein expression.…”

“…We next examined the differential expression of plasma proteins in healthy volunteers and IPF patients. In this recent proof of concept study, we employed hierarchical clustering of statistically significant differentially expressed proteins in IPF patients and healthy volunteers, demonstrating visually distinct plasma proteomes between healthy volunteers and IPF patients 37 (Fig. 4).…”

The role of periostin in lung fibrosis and airway remodeling

“…The speculation in the case of these mutations is that impaired or altered host defense may impair pathogen clearance and allow damage to the lung epithelium. Our recent work has also demonstrated that levels of circulating proteins associated with host defense response are downregulated in IPF patients further supporting impaired immunity as a key feature of disease pathology [57]. Given this supposition, it is especially interesting that recent studies have suggested that the lung microbiome is altered in patients with IPF.…”