The etiology of the disease is unknown, but abnormal oxidative stress has been implicated in the pathogenesis of scleroderma and linked to fibroblast activation. Platelet-derived growth factor (PDGF) seems to be a stimulator of the production of reactive oxygen species (ROS) which are key cell transducers of fibroblast proliferation and collagen gene expression . In more details, it has been observed that ROS generation is strictly related to Ha-Ras, and growth-factor activated extracellular signal-regulated kinases 1/2 (Ha-Ras, ERK1/2), with the Ha-Ras- ERK1/2-ROS circuitry amplified in scleroderma fibroblasts . In fact, over-expression of Ha-Ras or ERK 1/2 or high ROS levels induce collagen gene transcription and senescence in normal fibroblasts 6. Since platelet-derived growth factor (PDGF) can induce ROS and Ras-ERK1/2 signaling and since IgG derived from scleroderma patients (SSc IgG) react with human fibroblasts , Svegliati and co-workers sought Ha-Ras-ERK1/2 and ROS stimulatory molecules in the serum of scleroderma patients and provided evidence that serum of scleroderma patients contains stimulatory IgG autoantibodies directed to the PDGF receptor (PDGFR) 5. These autoantibodies trigger the PDGFR, which induces ROS via Ha-Ras and ERK 1/2 signaling and is ultimately responsible for fibroblast activation, a distinctive feature of scleroderma 5.