OP0090 Mitochondrial dna mutations and respiratory chain dysfunction in lung fibrosis of systemic sclerosis

Background Recent data have implemented reactive oxygen species (ROS) in the etiology of interstitial lung disease (ILD) in systemic sclerosis. Objectives To investigate a role of large-scale somatically acquired mutations in mitochondrial DNA (mtDNA) and consecutive respiratory chain dysfunction as a trigger of ROS formation and lung fibrosis. Methods Lung biopsies from patients with idiopathic interstitial pneumonitis and systemic sclerosis (n=31) were analysed for mitochondrial functions and compared with biopsies from 13 healthy controls (HC). From 17 patients we had simultaneous biopsies from the upper and lower lung. Results Malondialdehyde as a marker of ROS formation was increased in ILD (p=0.007). The median proportion of mtDNA containing the pathogenic common deletion was 22.5% in ILD patients, compared to 0% in HC. This translated into a 3.8-fold diminishment of mtDNA-encoded cytochrome c-oxidase (COX2), but not nucleus-encoded (COX4) respiratory chain subunits in ILD compared to controls (p Conclusions Our data support a role of mtDNA-mutations and consecutive respiratory chain dysfunction as a trigger and perpetuator of ROS formation in both, idiopathic interstitial pneumonitis and ILD of patients with systemic sclerosis. Disclosure of Interest None declared