Project Overview

The Northern California Scleroderma Research Consortium (NCSRC) consists of a group of investigators at UCSF and Stanford who collaborate on efforts to understand the clinical presentations of scleroderma patients and how they relate to disease pathogenesis.  

Dr. Wolters: Work in my laboratory has focused on understanding the pathobiology of scleroderma-associated interstitial lung disease (SSc-ILD) and whether it shares biological mechanisms with idiopathic pulmonary fibrosis (IPF), a genetically mediated, fibrotic lung disease that affects older individuals. We have shown that IPF is driven by telomere dysfunction leading to premature aging in lung epithelial cells (Wolters, et al. Lancet Resp Med 2018).  

Peripheral blood leukocyte telomere length (PBL-TL) correlates with loss of lung function and mortality in IPF patients, such that shorter telomeres are associated with poorer survival.  Over the past year, we examined whether PBL-TL is similarly associated with outcomes in patients with SSc-ILD. Interestingly, we found that a subset of SSc-ILD patients has short telomeres in their lung epithelial cells.  In addition, shorter PBL-TL is associated with greater loss of lung function (forced vital capacity) and progressive ILD in patients with SSc. These data suggest there is a subset of patients with SSc-ILD whose disease is driven by biological mechanisms (telomere dysfunction) commonly found in IPF patients.  We are now in the process of validating these findings in the Stanford arm of the NCSRC cohort. We are also investigating whether short telomeres are associated with other complications in scleroderma patients.

How this work will impact patients

Identifying clinical subtypes of patients with SSc-ILD advances understanding about variations in disease pathogenesis.  This information can then be leveraged to develop therapies targeting specific disease subtypes. It is especially important to identify those SSc-ILD patients with pathologic drivers similar to IPF, as they may be more responsive to the recently approved anti-fibrotic therapies for IPF patients.

Role of the Scleroderma Research Foundation

The SRF provides funding to support clinical coordinators and laboratory technicians who aid in patient recruitment, data and biological sample acquisition and processing, and molecular analyses for multiple collaborative projects of the NCSRC. The SRF also facilitates research meetings amongst the scleroderma investigators at UCSF and Stanford, which are essential to the success of the NCSRC.