The tumour necrosis factor-related apoptosis-inducing ligand-osteoprotegerin system in limited systemic sclerosis: a new disease marker?

Objective. To investigate the role of the TNF-related apoptosis-inducing ligand-osteoprotegerin (TRAIL-OPG) system in the pathogenesis of limited SSc (lSSc). Methods. Circulating levels of TRAIL and of its soluble receptor OPG were measured by ELISA in serum samples obtained from 50 lSSc patients and 50 healthy controls. Results. TRAIL serum levels in lSSc patients were similar to those of healthy controls, whereas the OPG serum levels were significantly increased (P < 0.0001). According to different subgroups of lSSc patients, TRAIL was not statistically different between each group and healthy controls; concerning OPG, the statistically different value was also maintained when comparing each single lSSc group with the whole control population. Conclusions. OPG serum levels, but not TRAIL, are elevated in lSSc patients. Since OPG binding to TRAIL inhibits TRAIL-TRAIL receptor interaction, the relative concentrations of these two molecules in the local micro-environment has to be considered. In this setting, OPG increase in lSSc patients may produce a detrimental effect by counteracting the vasoprotective activity of TRAIL. The TRAIL : OPG ratio and their relative levels of expression in lSSc patients should be taken into consideration as a possible novel marker of vascular damage.