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Published on: February 5, 2015
Tumour necrosis factor alpha mRNA expression in early multiple sclerosis lesions: correlation with demyelinating
A Bitsch1, T Kuhlmann, C Da Costa
1Klinik und Poliklinik für Neurologie, Abteilung Neurologie, Georg-August-Universität, Göttingen, Germany.
Abstract:
The precise role of tumour necrosis factor alpha (TNFalpha) in multiple sclerosis (MS) is still controversial. Most findings from the animal model experimental allergic encephalomyelitis have yet to be confirmed in multiple sclerosis. The aim of this study was to define the significance of TNFalpha with respect to the hallmark of MS, that is demyelination. Therefore, 78 lesion areas from diagnostic brain biopsies of 32 patients were analysed. Lesion demyelinating activity was classified by the presence of myelin degradation products in macrophages and macrophage activation markers. Non-radioactive in situ hybridisation was carried out to detect TNFalpha mRNA expressing cells. DNA fragmentation was visualised by TdT-mediated X-dUTP nick end labeling. A significantly higher number of cells expressed TNFalpha mRNA in active demyelinating lesions than in inactive or remyelinating lesions irrespective of the extent of the inflammatory infiltrate. TNFalpha mRNA expression correlated with the appearance of DNA fragmentation in T lymphocytes and oligodendrocytes within the lesions. In the periplaque white matter, expression of TNFalpha mRNA negatively correlated with oligodendrocyte numbers. These data support previous findings from animal models and in vitro experiments. Although not proving, the current study strongly suggests a pathogenic role of TNFalpha in demyelination in human multiple sclerosis and gives further support for TNFalpha-directed therapeutic strategies.
Insights
Tumor necrosis factor alpha (TNFalpha) plays a key role in multiple sclerosis (MS) demyelination. This study found higher TNFalpha mRNA in active MS lesions, suggesting its involvement in disease pathogenesis and supporting TNFalpha-targeted therapies.
Area of Science:
- Neuroimmunology
- Pathology of Multiple Sclerosis
Background:
- The role of tumor necrosis factor alpha (TNFalpha) in multiple sclerosis (MS) pathogenesis remains debated.
- Findings from animal models of MS often lack direct confirmation in human patients.
Purpose of the Study:
- To investigate the significance of TNFalpha in the demyelination characteristic of MS.
- To correlate TNFalpha expression with demyelinating activity and oligodendrocyte status in MS lesions.
Main Methods:
- Analysis of 78 lesion areas from brain biopsies of 32 MS patients.
- Assessment of demyelinating activity using myelin degradation products and macrophage markers.
- In situ hybridization for TNFalpha mRNA and TdT-mediated X-dUTP nick end labeling for DNA fragmentation.
Main Results:
- Significantly higher TNFalpha mRNA expression in active demyelinating MS lesions compared to inactive or remyelinating lesions.
- Correlation between TNFalpha mRNA expression and DNA fragmentation in T lymphocytes and oligodendrocytes.
- Negative correlation between TNFalpha mRNA expression and oligodendrocyte numbers in periplaque white matter.
Conclusions:
- The study provides strong evidence for a pathogenic role of TNFalpha in human MS demyelination.
- Results support findings from animal models and in vitro studies.
- Supports the rationale for TNFalpha-directed therapeutic strategies in MS.
