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 TRAF2 (TNF receptor-associated factor 2) and RIP (receptor-interacting protein) 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 RRMS patients longitudinally every 3 months over a 9-month time period.
Results: TRAF2 expression was significantly elevated in RRMS patients compared to the other disease courses (p<0.005, respectively) and the control group (p<0.009). RIP expression was significantly elevated in the patient groups compared to the healthy group (phealthy-RR<0.002; phealthy-PP<0.003; phealthy-SP<0.06). Neither variable changed over the 9-month time course.
Conclusion: TRAF2 and RIP1 elevation in leukocytes might be interpreted as the molecular equivalent of an elevated general inflammatory activity in MS patients compared to healthy control persons. TRAF2 elevation in RRMS reinforces the concept that different pathophysiological and immunological processes sustain RRMS and SPMS or PPMS.
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