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Shedding of TNF receptors in multiple sclerosis patients
A M Jurewicz1, A K Walczak, K W Selmaj
1Department of Neurology, Medical University of Lodz, Poland.
Objective:
To evaluate the rate of shedding of tumor necrosis factor (TNF) receptors (TNFRs) in MS patients.
Background:
It was previously suggested that TNF might play a significant role in the immunopathologic mechanism of MS. TNF mediates its biologic effects by interacting with two distinct receptors: TNFR-p55 and TNFR-p75. Both of these receptors exist in soluble and membrane-bound forms. Soluble receptors have been shown to influence TNF activity in vitro and in vivo and maintain balance between active, free TNF and inactive form of this cytokine bound to its soluble receptors.
Methods:
In the current study, the authors measured shedding of TNFRs from cell surface of peripheral blood mononuclear cells, peripheral blood lymphocytes, and monocytes in three groups of MS patients: relapsing-remitting in relapse, relapsing-remitting in remission, and chronic progressive.
Results:
The authors observed a significant distortion in generation of both soluble TNF receptors. Whereas the TNFR-p55 was shed at lower rate compared with healthy volunteers, the shedding of TNFR-p75 was significantly higher in MS patients.
Conclusion:
Disturbance in TNFR shedding might contribute to the distortion of a fine balance between circulating TNF and its natural inhibitors in MS.
Insights
Tumor necrosis factor (TNF) receptor shedding is altered in multiple sclerosis (MS) patients. TNFR-p75 shedding is higher, while TNFR-p55 shedding is lower, potentially disrupting TNF regulation in MS.
Area of Science:
- Immunology
- Neuroscience
- Biochemistry
Background:
- Tumor necrosis factor (TNF) is implicated in multiple sclerosis (MS) pathogenesis.
- TNF exerts effects via TNFR-p55 and TNFR-p75, which exist in soluble and membrane-bound forms.
- Soluble TNF receptors (sTNFRs) modulate TNF activity and cytokine balance.
Purpose of the Study:
- To quantify the shedding rates of TNF receptors (TNFRs) in patients with multiple sclerosis (MS).
- To compare TNFR shedding between different MS disease courses and healthy controls.
Main Methods:
- Measured shedding of TNFRs from peripheral blood mononuclear cells, lymphocytes, and monocytes.
- Studied three MS patient groups: relapsing-remitting (relapse), relapsing-remitting (remission), and chronic progressive.
- Compared shedding rates to those of healthy volunteers.
Main Results:
- Observed significant alterations in soluble TNFR generation in MS patients.
- TNFR-p55 shedding was reduced compared to healthy controls.
- TNFR-p75 shedding was significantly elevated in MS patients.
Conclusions:
- Altered TNFR shedding contributes to dysregulated TNF and its inhibitors in MS.
- This imbalance may play a role in the immunopathogenesis of MS.
- Further research into TNFR dynamics could reveal therapeutic targets for MS.