Apoptosis mediators FasL and TRAIL are upregulated in peripheral blood mononuclear cells in MS

Objective: To investigate the expression of apoptosis-inducing- ligand and receptor molecules in patients with MS. Background: Dysregulation of apoptosis may induce autoimmune conditions, possibly through inadequate termination of immune responses, and could be of importance for pathogenesis of MS. Methods: Messenger RNA (mRNA) levels of two apoptosis-related members of the tumor necrosis factor (TNF) receptor family, Fas and TNF-related apoptosis-inducing ligand (TRAIL) receptor 2 (TRAIL-R-2), and their ligands, Fas ligand (FasL) and TRAIL, were quantified by competitive reverse transcription PCR in unstimulated peripheral blood mononuclear cells in 47 untreated patients with MS and 46 control subjects, Results: The expression of FasL was increased in patients with MS compared with healthy control subjects. Analysis of clinical subgroups revealed that the increase was marked in relapsing-remitting MS, being especially high in remission (p = 0.0002), but less so in chronic progressive MS (p = 0.14). Compared with healthy control subjects, TRAIL mRNA levels were also upregulated in patients with MS (p = 0.0001) but did not differ between clinical subgroups. The expression of TRAIL-R, was slightly elevated in patients with MS (p = 0.02) whereas the expression of Fas was similar in patients and control subjects. The ratio of expression levels for two isoforms of TRAIL-R,, TRICK2a and TRICK2b, in patients with MS differed from healthy control subjects (p = 0.04). Conclusions: There was increased expression of both FasL and TRAIL in peripheral blood lymphocytes. It remains to be determined whether this increased expression represents a disease-promoting autoimmune process or is merely the effect of a secondary compensatory mechanism that downregulates the inflammatory response.