Objective. Scleroderma, also known as systemic sclerosis (SSc), is a chronic, life-threatening autoimmune disease characterized by a wide spectrum of manifestations and a variable evolution. The presence of particular antinuclear antibodies is often predictive of the clinical expression and prognosis of the disease, but the molecular mechanisms of the immune responses remain unclear. Recently, we have shown xenobioticinduced recruitment of nuclear autoantigens to proteasomes in the cell nucleus in cell culture and in animal models in correlation with a unique autoantibody response. In this study, we attempted to validate our findings in patients with SSc.Methods. Using indirect immunofluorescence microscopy, run-on replication and transcription assays, immunoblotting, and proteasome activity assays, we analyzed the nuclear structure, function, and proteasomal proteolysis in HEp-2 cells treated with xenobiotics or left untreated. Blood dendritic cells (DCs) were isolated from 30 patients with SSc and age-and sexmatched control subjects to determine the subcellular localization of SSc autoantigens in relation to proteasomes. Results. Xenobiotics induced a relocation of the