Abstract
Introduction:Systemic sclerosis is an autoimmune connective tissue disease in which there is activation of the immune system, vascular disease and fibrosis. Activation of quiescent fibroblasts to myofibroblasts is key to disease pathogenesis. Gremlin-1 is a bone morphogenetic protein antagonist which is important in development and we recently reported in skin fibrosis. The aim of this study was to determine the serum circulating levels of Gremlin-1 in early diffuse systemic sclerosis.Methods:Twenty-one early diffuse systemic sclerosis patients (less than 2 years from first non-Raynaud’s symptom) were included and age and sex-matched healthy controls. Serum was isolated from blood and measured with a specific enzyme-linked immunoassay for Gremlin-1. Clinical variables were also measured.Results:Significantly elevated Gremlin-1 was found in sera of early diffuse systemic sclerosis patients (p < 0.001). In patients with interstitial lung disease, this compared to systemic sclerosis without evidence of interstitial lung disease, Gremlin-1 was significantly elevated (p < 0.0007). A correlation was found between circulating Gremlin-1 and modified Rodnan Skin Score, albeit weak.Discussion:In early diffuse systemic sclerosis patients, elevated Gremlin-1 is found in serum. This is particularly prominent in systemic sclerosis–associated interstitial lung disease. This suggests that Gremlin-1 may be a biomarker for systemic sclerosis interstitial lung disease.
Highlights
Systemic sclerosis is an autoimmune connective tissue disease in which there is activation of the immune system, vascular disease and fibrosis
We described very recently that overexpression of Gremlin-1 led to increased myofibroblast transition that was partially dependant on transforming growth factor (TGF)-β1 signalling, as blockade of TGF-β1 mitigated fibrosis.[11]
We have recently described a pro-fibrotic role of Gremlin-1 in dermal fibrosis in Systemic sclerosis (SSc)
Summary
Systemic sclerosis is an autoimmune connective tissue disease in which there is activation of the immune system, vascular disease and fibrosis. The aim of this study was to determine the serum circulating levels of Gremlin-1 in early diffuse systemic sclerosis. Results: Significantly elevated Gremlin-1 was found in sera of early diffuse systemic sclerosis patients (p < 0.001). In patients with interstitial lung disease, this compared to systemic sclerosis without evidence of interstitial lung disease, Gremlin-1 was significantly elevated (p < 0.0007). Discussion: In early diffuse systemic sclerosis patients, elevated Gremlin-1 is found in serum. This is prominent in systemic sclerosis–associated interstitial lung disease. This suggests that Gremlin-1 may be a biomarker for systemic sclerosis interstitial lung disease. Activation of quiescent fibroblasts to activated myofibroblasts that secrete copious amounts of extracellular matrix is at the core of the disease, and understanding of how these cells are activated remains elusive
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