Personalising treatment in idiopathic pulmonary fibrosis

December 19, 2013
Masson-trichrome staining of lung sections from TLR3-/- mice shows increased collagen deposition

Researchers in UCD Conway Institute have identified a potential biomarker of rapidly progressive pulmonary fibrosis and pinpointed a defective molecular function as a potential therapeutic target.

Planning treatment for patients with idiopathic pulmonary fibrosis (IPF) is difficult due to the unpredictable course the disease can take. Almost 15% of IPF patients die within 12 months of the initial diagnosis.

However, researchers led by Conway Fellow, Professor Seamas Donnelly of UCD School of Medicine & Medical Science and the Education & Research Centre, St Vincent's University Hospital have identified a potential biomarker of rapidly progressive disease and pinpointed a defective molecular as a potential .

Idiopathic pulmonary fibrosis (IPF) is a fatal progressive interstitial pneumonia. This chronic inflammatory disease leads to the breakdown of normal lung architecture and the loss of lung function as a result.

In humans, the innate immune system is responsible for recognising tissue injury and infection. Toll-like receptor 3 (TLR3) is an innate immune system receptor involved in this process of identifying pathogens and defending against them.

Professor Donnelly and his team investigated whether a particular genetic defect in the TLR3 gene might disrupt the normal inflammatory response in IPF and accelerate the progression of the disease.

This specific genetic variation in one of component DNA building blocks of the TLR3 gene is named L412F single-nucleotide polymorphism (SNP).

The UCD research team in collaboration with colleagues in Ireland, the UK and in the USA examined the impact of defective TLR3 function in the lung and on the progression of IPF using lung fibroblasts from patients with and without TLR3 L412F single-nucleotide polymorphism (SNP) and in a laboratory model of the disease.

Commenting on the results, Dr Gordon Cooke, senior postdoctoral research fellow and one of the authors of the recently published article said, "This study identifies the TLR3 L412F polymorphism as a potential marker of rapidly and defective TLR3 function represents a potential therapeutic target in IPF."

Professor Seamas Donnelly said, "Our findings suggest a strong mechanistic link between this candidate polymorphism and altered fibrosis, the immune response, and survival in patients. This opens the possibility of focused therapies aimed at restoring TLR3 function as well as supporting an approach to personalising therapy in IPF by identifying at an early stage those patients at significant risk and tailoring their accordingly."

Patient cohorts from around the world were used to validate the study including those from St. Vincent's University Hospital, Dublin. Genotyping of was carried out in the UCD Conway genomics core facility. The research is supported by funding from the Health Research Board of Ireland, Science Foundation Ireland and the Irish Lung Foundation.

Explore further: Newly identified biomarkers help predict outcome in idiopathic pulmonary fibrosis

More information: Dwyer DN, Armstrong ME, Cooke G, Keane MP, Donnelly SC, et al. The Toll-like Receptor 3 L412F Polymorphism and Disease Progression in Idiopathic Pulmonary Fibrosis. American Journal of Respiratory & Critical Care Medicine. 188; 12, 1442-1450. December 15, 2013.

Related Stories

Gene study helps understand pulmonary fibrosis

April 16, 2013

A new study looking at the genomes of more than 1,500 patients with idiopathic pulmonary fibrosis, a rare and devastating lung disease, found multiple genetic associations with the disease, including one gene variant that ...

Finding cellular causes of lung-hardening disease

September 17, 2013

(Medical Xpress)—Idiopathic Pulmonary Fibrosis, or IPF, is an incurable lung disease that, over time, turns healthy lung tissue into inflexible scar tissue – hardening the lungs and eventually causing respiratory distress ...

Recommended for you

Zika virus infection alters human and viral RNA

October 20, 2016

Researchers at University of California San Diego School of Medicine have discovered that Zika virus infection leads to modifications of both viral and human genetic material. These modifications—chemical tags known as ...

Food-poisoning bacteria may be behind Crohn's disease

October 19, 2016

People who retain a particular bacterium in their gut after a bout of food poisoning may be at an increased risk of developing Crohn's disease later in life, according to a new study led by researchers at McMaster University.

Neurodevelopmental model of Zika may provide rapid answers

October 19, 2016

A newly published study from researchers working in collaboration with the Regenerative Bioscience Center at the University of Georgia demonstrates fetal death and brain damage in early chick embryos similar to microcephaly—a ...

Scientists uncover new facets of Zika-related birth defects

October 17, 2016

In a study that could one day help eliminate the tragic birth defects caused by Zika virus, scientists from the Florida campus of The Scripps Research Institute (TSRI) have elucidated how the virus attacks the brains of newborns, ...

Ebola drug ZMapp may help, but is not a miracle cure

October 13, 2016

ZMapp, once touted as a miraculous "secret serum" against the deadly Ebola virus, has shown some success but fell short of the bar for effectiveness in a clinical trial, researchers said Wednesday.


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.