Skin Gene Expression Correlates of Severity of Interstitial Lung Disease in Systemic Sclerosis

Autor: Carol Feghali-Bostwick, Jeffrey T. Chang, Julio Charles, Minghua Wu, Dinesh Khanna, Filemon K. Tan, Tiffany A. Graham, Emma C. Ferguson, Shervin Assassi, Maureen D. Mayes, Daniel E. Furst
Rok vydání: 2013
Předmět:
Zdroj: Arthritis & Rheumatism. 65:2917-2927
ISSN: 0004-3591
DOI: 10.1002/art.38101
Popis: Systemic sclerosis (SSc) is characterized by the triad of vasculopathy, immune dysregulation, and fibrosis and is associated with high morbidity and mortality. Interstitial lung disease (ILD) is the primary cause of SSc-related mortality (1,2), and the available treatment options for this disease manifestation have limited efficacy (3,4). Furthermore, the course of lung involvement in SSc is highly variable. Even though deterioration of pulmonary function is slowly progressive in many SSc patients, ~15% have a rapidly progressive course (5). Clinicians are currently unable to predict reliably early in the course of disease which patients will develop significant ILD. Therefore, the treatment of SSc-related ILD is delayed until fibrosis has clearly occurred in the pulmonary tissue. Gene expression profiling of affected end organs has provided a valuable resource for development of biomarkers in the field of oncology. Although the lung is a prominently affected end organ in SSc, its inaccessibility has precluded the widespread use of pulmonary tissue for research and clinical purposes. The global gene expression profile of SSc pulmonary tissue has only been studied in patients with end-stage disease undergoing lung transplantation (6). Skin is another prominently affected and easily accessible organ in patients with SSc. Global gene expression studies of the skin tissue of patients with SSc have demonstrated a distinct gene expression profile compared to controls; an inflammatory activation pattern and a fibrotic signature were seen (7,8). In a larger study with 24 SSc patients, patients with diffuse cutaneous SSc (dcSSc) could be subdivided into 3 distinct groups and patients with limited cutaneous SSc (lcSSc) into 2 groups based on skin gene expression profiling. A subgroup of patients with lcSSc and dcSSc showed a pattern of inflammatory genes that included interferon-inducible genes (9) and interleukin-13 (IL-13)–inducible genes (10). Another subgroup of SSc patients with diffuse skin involvement showed a fibrotic gene expression profile containing transforming growth factor β (TGFβ)–responsive genes (11). In that study, none of the patients with dcSSc in the subgroup without activation of TGFβ response genes had ILD (defined as a dichotomous outcome based on high-resolution computed tomography [HRCT] results). There are no published reports of skin transcript correlates of severity of ILD in patients with SSc. In the present study, we investigated the skin transcript correlates of ILD severity in a large group of patients with SSc. Considering that skin tissue can be obtained during routine clinical practice, the results of the present hypothesis-generating study can provide valuable information for identification of novel biomarkers and therapeutic targets.
Databáze: OpenAIRE
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