Scleroderma

Pulmonary Fibrosis (PF) and Pulmonary Arterial Hypertension (PAH) are incurable rare lung diseases and are the leading cause of mortality in patients with Systemic Sclerosis (SSc). However patients might have a reason to breathe easier since researchers from the University of Pittsburgh now provide a novel insight that explains how Systemic Sclerosis develops.

Systemic Sclerosis (SSc) is a rare autoimmune disease which affects the connective tissue of the skin and internal organs, such as lungs, kidneys or heart. It is often accompanied by pulmonary complications, Pulmonary Fibrosis (PF) and Pulmonary Arterial Hypertension (PAH), for which therapies have only a low benefit and patients often require a lung transplantation. Despite previous research, how the disease develops remains poorly understood.

How SSc develops has eluded researchers, because they have lacked the necessary samples of affected tissue from patients. That is why Dr. Carol A. Feghali-Botswick’s research team from the University of Pittsburgh School of Medicine started collecting lung tissue samples from affected patients.

“The challenge was collecting a critical number of lung tissues from patients with SSc,” said Dr. Carol A. Feghali-Botswick. A certain number of lung tissue samples from patients with Systemic Sclerosis was necessary to obtain good results, but as lung biopsies are not routinely done the availability was fairly limited.

“We started banking these tissues in the mid-1990s and had to wait until we accrued a sufficient number,” explained Dr. Feghali-Botswick. “The University of Pittsburgh Medical Center has a vibrant lung transplant program and transplants more SSc patients than anywhere else in the country or the world, so we were uniquely poised to do this study once we had enough patients donate their lungs.” Finally they managed to analyze lung tissues samples from 33 patients with SSc who underwent lung transplantations. They created a list of characteristics, so called gene expression profiles, which were unique or shared throughout the samples.

With the data in hand, Dr. Feghali-Botswick’s team was able to generate signatures that were specific for SSC as well as signatures that were specific for the two complications: Pulmonary Fibrosis (PF) and Pulmonary Arterial Hypertension (PAH). These signatures provided Dr. Feghali-Botswick’s team with insights to genes that might be involved in causing SSc.

To follow up this successful work the researchers are continuing the next phase of the project. “We are currently looking at some of the genes identified through the analysis to determine if they can serve as markers of lung disease in SSc, and possibly even as predictors of lung involvement.“

Markers, such as biomarkers, are substances used to examine an organ’s function or other aspects of health. It is an important tool in diagnostics that allows for easy disease detection, limits the risks of misdiagnosis and also reduces the costs needed for treatment.

In the ongoing search for potential markers, Dr. Feghali-Botswick told CheckOrphan, “Some patients have serum samples obtained prior to the onset of their lung disease as well as following the diagnosis of lung involvement”. This way the researchers will be able to measure the proteins in the serum and to see if some of the protein levels increase prior to the onset of lung involvement or only following the development of lung disease.

“In the long run, this will allow us to develop a panel of proteins we can use for screening patients at risk of developing lung disease with the goal of initiating treatment very early when it's likely to be more effective,” Dr. Feghali-Botswick said.

“I would like to emphasize that none of this work would have been possible without the generosity of our patients who are always willing to donate blood, skin biopsies and lung tissues following lung transplantation surgery.“

Malisova, B. (2011), "New Hope for Patients With Rare Lung Diseases, Systemic Sclerosis (SSc)"; original article can be accessed here.