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TACE mRNA expression in peripheral mononudear cells precedes new lesions on MRI in multiple sclerosis
T Seifert1, B C Kieseier, S Ropele
1Department of Neurology, Karl Franzens University, Auenbruggerplatz 22, Graz A-8036, Austria. thomas.seifert@kfunigraz.ac.at
Abstract:
Tumor necrosis factor-alpha (TNF-alpha) is involved in the pathogenesis of multiple sclerosis (MS). It has to be released from its cell membrane-bound precursor by proteolytic cleavage. This is mainly performed by a member of the ADAM (a disintegrin and metalloproteinase) family of enzymes, TNF-alpha-converting enzyme (TACE, ADAM 17). In a longitudinal study on 11 relapsing-remitting MS patients, we qualitatively determined mRNA expression of TNF-alpha and TACE in peripheral blood mononuclear cells (PBMCs) without ex vivo stimulation. mRNA expression was related to disease activity as assessed by monthly gadolinium (Gd)-enhanced brain magnetic resonance imaging (MRI). Patients found positive for TACE mRNA in PBMCs showed a significantly higher mean number of new Gd-enhancing lesions per scan one month following PBMC sampling.
Insights
Tumor necrosis factor-alpha (TNF-alpha) is key in multiple sclerosis (MS) pathogenesis. TACE mRNA in patient blood cells correlated with new MRI lesions, indicating disease activity.
Area of Science:
- Neuroimmunology
- Molecular Biology
- Enzymology
Background:
- Tumor necrosis factor-alpha (TNF-alpha) plays a role in multiple sclerosis (MS) pathogenesis.
- TNF-alpha is released from its precursor by TNF-alpha-converting enzyme (TACE, ADAM 17).
Purpose of the Study:
- To investigate the relationship between TACE mRNA expression in peripheral blood mononuclear cells (PBMCs) and MS disease activity.
- To qualitatively assess mRNA levels of TNF-alpha and TACE in relapsing-remitting MS patients.
Main Methods:
- Longitudinal study involving 11 relapsing-remitting MS patients.
- Qualitative mRNA expression analysis of TNF-alpha and TACE in PBMCs without ex vivo stimulation.
- Correlation of mRNA expression with monthly gadolinium (Gd)-enhanced brain MRI scans.
Main Results:
- Patients positive for TACE mRNA in PBMCs showed a significantly higher mean number of new Gd-enhancing lesions per scan.
- One month following PBMC sampling, TACE mRNA positivity was linked to increased MRI-detected disease activity.
Conclusions:
- TACE mRNA expression in PBMCs may serve as a biomarker for predicting MS disease activity.
- This finding highlights the potential role of TACE in MS pathogenesis and disease monitoring.