Increased neoepitope concentrations linked with idiopathic pulmonary fibrosis progression
Protein fragments generated by metalloproteinase activity identified individuals with idiopathic pulmonary fibrosis from healthy controls, and the rate of fragment change was associated with disease worsening and reduced survival, according to recent study results.
“We believe that these neoepitopes have the potential to address an urgent unmet need in the management of idiopathic pulmonary fibrosis,” R. Gisli Jenkins, PhD, of the University of Nottingham in the United Kingdom, and colleagues wrote. “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.”
The researchers conducted an ongoing prospective, multicenter, observational cohort study of 189 participants with a confirmed diagnosis of idiopathic pulmonary fibrosis between September 2010 and March 2012.
Six neoepitopes were higher at baseline in individuals with progressive (n = 32) disease than in those with stable disease (n = 23). In this cohort, one neoepitope (CRPM) was linked with decreased survival time (HR = 3.74; 95% CI, 1.46-9.58).
Eight neoepitopes (BGM, C1M, C3A, C3M, C5M, C6M, CRPM, and VICM) were measured in a validation cohort of 134 individuals with idiopathic pulmonary fibrosis and 50 age-matched and sex-matched healthy controls.
An increasing rate of biomarker change in 3 months for BGM (HR = 1.845; 95% CI, 0.989-3.442), C1M (HR = 2.135; 95% CI, 1.14-3.999), C3M (HR = 1.708; 95% CI, 0.913-3.195), C5M (HR = 1.855; 95% CI, 1.003-3.432), C6M (HR = 2.145; 95% CI, 1.127-4.085), and CRPM (HR = 2.159; 95% CI, 1.146-4.069) indicated poorer overall survival.
The researchers said the study had limitations.
“Because the discovery cohort was enriched for individuals with extremes of disease severity, the validation cohort contains a disproportionate number of participants with moderate disease,” they wrote.
Disclosure: Jenkins reports receiving industry-academic funding from Biogen Idec, GlaxoSmithKline and Novartis. Jenkins also reports consultancy or speaker fees from Biogen Idec, Boehringer Ingelheim, InterMune, MedImmune, PPD, Pulmatrix and GlaxoSmithKline. Please see the full study for a list of all other authors’ relevant financial disclosures.