Researchers Discover Potential Biomarkers for Identifying IPF Disease Progression

Researchers Discover Potential Biomarkers for Identifying IPF Disease Progression

shutterstock_212535784A new study recently published in the journal The Lancet Respiratory Medicine revealed potential biomarkers for accurately assessing idiopathic pulmonary fibrosis (IPF) disease progression. The study is entitled “Longitudinal change in collagen degradation biomarkers in idiopathic pulmonary fibrosis: an analysis from the prospective, multicentre PROFILE study.

IPF is a rare, fatal lung disease in which the alveoli and lung tissues are damaged, turning thick and scarred (fibrosis) and compromising the oxygen transfer between the lungs and the bloodstream. IPF is characterized by shortness of breath (dyspnea) that gradually worsens and a persistent cough. There is no cure for this disease and respiratory failure is the main cause of death. IPF has a poor prognosis and the majority of the patients live three to five years after being diagnosed.

There is an urgent need for IPF biomarkers that can assess disease activity and aid clinicians and patients in management of the disease. In this study, researchers focused on possible extracellular matrix (ECM) biomarkers as predictors of disease progression.

The research team conducted an ongoing prospective, multicenter, observational cohort study called PROFILE (registered under the ClincialTrials.gov codes NCT01134822 and NCT01110694), which included patients from two centers in the United Kingdom who were diagnosed with IPF or idiopathic non-specific interstitial pneumonia between September 2010 and March 2012. Serum samples from the participants were collected at baseline as well as after one month, three months and six months and analyzed for the presence of matrix metalloprotease (MMP)-degraded ECM proteins through a technique called ELISA-based neoepitope assay.

Researchers found that in the 189 eligible participants (134 patients and 50 healthy controls), seven protein fragments generated by metalloproteinase activity (neoepitopes BGM, C1M, C3M, C6M, CRPM, ELM2 and VICM) differed significantly between IPF patients and healthy controls. Six neoepitopes (C1M, C3A, C3M, C6M, CRPM, and VICM) were found in higher concentrations at baseline in individuals with progressive IPF than in individuals with stable IPF. C1M and C3A baseline concentrations were associated with increased mortality. After six months, five of these neoepitopes (C1M, C3A, C3M, C6M and CRPM) plus BGM were found to be higher in patients with progressive IPF. In addition, the rate of neoepitope concentration changed after 3 months in six biomarkers (BGM, C1M, C3M, C5M, C6M, and CRPM) and was found to be associated with increased disease severity and poorer overall survival, with CRPM being the strongest predictor of the six.

The research team concluded that the concentration of certain neoepitopes generated by MMP activity is increased in IPF patients’ serum and that this increase is linked to disease progression and survival rate, suggesting that neoepitope measurements can be potentially used as biomarkers to assist IPF disease management. “We believe that these neoepitopes have the potential to address an urgent unmet need in the management of idiopathic pulmonary fibrosis,” concluded the research team. “Increasing concentrations of matrix neoepitopes could identify a phenotype of idiopathic pulmonary fibrosis characterized by rapid matrix turnover and poor prognosis, which might be more amenable to antifibrotic therapy.”

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