FADD Is Upregulated in Relapsing Remitting Multiple Sclerosis

Abstract

Objective: To elucidate the role of tumor necrosis factor (TNF) receptor signal transduction in multiple sclerosis (MS). Methods: We performed a cross-sectional analysis of the gene expression of TNF receptor-associated death domain protein (TRADD) and Fas-associated death domain protein (FADD) in peripheral blood leukocytes of 23 relapsing remitting (RR), 19 secondary progressive (SP) and 12 primary progressive (PP) MS patients, as well as of 29 healthy controls by quantitative RT-PCR. Additionally, we monitored a subgroup of 15 RR MS patients longitudinally every 3 months over the time period of 9 months. Results: FADD expression was significantly elevated in RR MS patients compared to the other disease courses (p < 0.048). The median of FADD expression was elevated in the RR MS patient groups compared to the healthy group, but this was not significant (p < 0.053). The median of TRADD expression was elevated in the patient groups compared to the healthy group, but this was not significant (p < 0.14). Neither variable changed significantly over the time course of 9 months. Conclusion: FADD elevation in leukocytes might be interpreted as the molecular equivalent of an elevated general inflammatory activity in RR MS patients compared to other disease courses. FADD elevation in RR MS reinforces the concept that different pathophysiological and immunological processes sustain RR MS and SP or PP MS.

Heritability Estimation of Multiple Sclerosis Related Plasma Protein Levels in Sardinian Families with Immunochip Genotyping Data

“…Finally, the Fas-associated death domain protein (Fadd) ( = 0.41) is a molecule that interacts with various cell surface receptors and can be activated by members of the tumor necrosis factor receptor family to transmit apoptotic signals [ 59 ]. An increased expression of FADD was found in peripheral blood leukocytes of RR-MS patients highlighting an elevated general pro-inflammatory activity [ 60 ]. The increased Fadd regulation has also been observed in the grey matter of MS patients compared to controls [ 61 ].…”

Cytokines and Transgenic Matrix in Autoimmune Diseases: Similarities and Differences

“…TNFα adapter proteins ↑ FADD mRNA in leukocytes [66] ↑TRAF2 mRNA in leukocytes [67] ↓TRADD, FADD, RIP-1, TRAF-2 mRNA in PBMC [123] expression. Some kinds of dysregulation in cell functioning can be common in different autoimmune diseases.…”

“…TNFα signal transduction in lymphocytes is altered in multiple sclerosis. Fas-associated death domain protein (FADD) gene expression was upregulated in leukocytes from RRMS patients compared to SPMS, PPMS and healthy controls [66]. TRAF2 (TNF receptor-associated factor 2) gene expression was increased in leukocytes of RRMS patients compared to other MS forms and healthy controls.…”

The Possible Role of Neural Cell Apoptosis in Multiple Sclerosis

“…Rinta et al reported that the Fas-ligand was increased in the sera of RRMS patients during relapse [ 41 ]. In addition, the extrinsic pathway adaptor, FADD, was shown to be upregulated in RRMS individuals [ 42 ]. The switch from clinically isolated syndrome (CIS) to MS, in a cohort consisting of a limited number of patients, was associated with a different profile of apoptosis-related gene transcription in comparison with no converting CIS patients [ 43 ].…”