The role of regulatory T cells in familial Mediterranean fever (FMF)
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Published on: January 7, 2019
D Rimar1, I Rosner, G Slobodin
1Rheumatology Unit, Bnai Zion Medical Center, POB 4940, Haifa 31048, Israel. doronrimar@gmail.com
Abstract:
The role of regulatory T cells (T-regs) in familial Mediterranean fever (FMF) was never evaluated. Preliminary studies that we have conducted suggested a rise in the number of regulatory T cells after FMF attacks reaching a maximal level at 7 days. The aim of this study was to evaluate the percentage and activity of regulatory T cells in FMF. Six patients with refractory FMF and six healthy controls were evaluated. The percentage of T-reg cells and forkhead box protein 3 (Foxp3) expression was evaluated and compared between four states: FMF in remission, FMF at the first day of an attack, FMF 7 days after the start of the attack, and healthy controls. Four females and two males were included. All patients had FMF with high severity score, 2.8 ± 0.4 (0-3). The mean age was 31.6 ± 6.2. The mean age at onset was 9.3 ± 9.3. The mean colchicine dose was 2.6 mg ± 0.4. The expression of Foxp3 7 days after the attacks was significantly higher than in FMF at the first day of the attack, FMF in remission, and healthy controls 10.08 ± 2.36 vs. 7.005 ± 0.3 vs. 5.3 ± 1.06 vs. 4.44 ± 1.8; p < 0.05 (Fig.1). The percentage of T-regs in peripheral blood was not statistically different between the four groups. Theexpression of Foxp3 by T-regs increases 7 days after attacks of FMF. Anti-inflammatory cytokines interleukin-10 and TGF-β are known to activate T-regs and have been reported to increase in FMF attacks in line with the present findings. It is suggested that T-regs may have a role in terminating FMF attacks.
Insights
Regulatory T cells (T-regs) show increased activity, specifically higher Foxp3 expression, seven days after Familial Mediterranean Fever (FMF) attacks, suggesting a role in resolving FMF flares.
Area of Science:
- Immunology
- Rheumatology
- Genetics
Background:
- Familial Mediterranean Fever (FMF) is a genetic autoinflammatory disorder characterized by recurrent inflammatory attacks.
- The role of regulatory T cells (T-regs) in FMF pathogenesis and resolution remains largely unexplored.
Purpose of the Study:
- To investigate the percentage and functional activity of T-regs in patients with FMF during different disease states.
- To compare T-reg activity between FMF patients in remission, during acute attacks, and in healthy controls.
Main Methods:
- Evaluated six refractory FMF patients and six healthy controls.
- Assessed T-reg cell percentage and Forkhead box protein 3 (Foxp3) expression in four conditions: FMF remission, day 1 of attack, 7 days post-attack, and healthy controls.
- Analyzed Foxp3 expression levels and T-reg percentages in peripheral blood.
Main Results:
- Foxp3 expression by T-regs was significantly higher 7 days after FMF attacks compared to day 1 of attack, remission, and healthy controls (p < 0.05).
- The overall percentage of peripheral T-regs did not differ significantly between the four groups.
- Findings align with increased anti-inflammatory cytokines (IL-10, TGF-β) observed during FMF attacks.
Conclusions:
- T-reg activity, indicated by Foxp3 expression, increases following FMF attacks.
- T-regs may play a crucial role in the natural resolution and termination of FMF attacks.
- Further research into T-reg modulation could offer novel therapeutic strategies for FMF.
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