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Increased neutrophil apoptosis during attacks of familial Mediterranean fever
1Department of Pediatric Nephrology and Rheumatology, Hacettepe University Faculty of Medicine, Sihhiye 06100 Ankara, Turkey.
Aim:
Apoptosis is a programmed form of cell death. Recently much attention has been devoted to the role of apoptosis in rheumatological diseases. We have aimed to analyze apoptosis in the inflammatory pathway of familial Mediterranean fever (FMF).
Methods:
26 FMF patients and 12 age and sex matched controls were the subject of the study. Twelve of the patients were analyzed during an FMF attack whereas samples were obtained at least a week after an attack in 14. Four of the patients had renal amyloidosis. Whole blood was treated with ammonium chloride for RBC lysis. Subsequently the cells were stained with propidium iodide and annexin. Neutrophils and lymphocytes were gated separately for analysis by flow cytometry. We have also analyzed cellular Fas and Fas-ligand expression in these cells.
Results:
The mean age of the patients was 12.00 +/- 3.17, and was not different than the control subjects. Erythrocyte sedimentation rate and CRP levels were significantly elevated in the attack group as compared to the attack-free group. The mean levels of neutrophil apoptosis in the FMF patients with an attack, attack-free and controls were 12.94 +/- 11.78, 6.60 +/- 7.83 and 3.98 +/- 4.27, respectively. Lymphocyte apoptosis in the same groups were 7.84 +/- 8.63, 2.75 +/- 2.33, and 1.22 +/- 0.93, respectively. Neutrophil and monocyte apoptosis was significantly increased during the attack as compared to the controls (p < 0.05). However lymphocyte apoptosis was not different between the aforementioned groups. On the other hand, lymphocyte apoptosis was significantly increased in the SLE patients (p < 0.05), whereas neutrophil apoptosis was not. Fas staining of neutrophils were not different between the groups (p > 0.05). On the other hand the difference between the groups for FasL was significant (p < 0.05).
Conclusion:
Neutrophil and monocyte but not lymphocyte apoptosis was significantly increased during FMF attacks reminding us that FMF is an autoinflammation of certain peripheral cells. The increased apoptosis in these patients maybe regarded as a response to clear the unwanted inflammatory cells. On the other hand the increased apoptosis maybe the explanation of the self-limited nature of the FMF attacks. Future studies will enlighten us on the significance of this increased apoptosis in the process of inflammation.
Insights
Familial Mediterranean fever (FMF) attacks show increased neutrophil and monocyte apoptosis, but not lymphocyte apoptosis. This heightened cell death may explain the self-limiting nature of FMF attacks and the removal of inflammatory cells.
Area of Science:
- Immunology
- Cell Biology
- Rheumatology
Background:
- Apoptosis, or programmed cell death, plays a role in rheumatological diseases.
- Familial Mediterranean fever (FMF) is an autoinflammatory disorder characterized by recurrent inflammatory attacks.
Purpose of the Study:
- To analyze the role of apoptosis in the inflammatory pathway of Familial Mediterranean Fever (FMF).
Main Methods:
- Flow cytometry was used to analyze apoptosis in neutrophils and lymphocytes from 26 FMF patients and 12 controls.
- Fas and Fas-ligand expression were also assessed in these cells.
- Patients were studied during FMF attacks and in attack-free periods.
Main Results:
- Neutrophil and monocyte apoptosis were significantly increased during FMF attacks compared to controls.
- Lymphocyte apoptosis was not significantly different between FMF patients and controls, but was increased in Systemic Lupus Erythematosus (SLE) patients.
- Fas expression on neutrophils did not differ, but Fas-ligand expression showed significant differences between groups.
Conclusions:
- Increased neutrophil and monocyte apoptosis during FMF attacks suggests a role in clearing inflammatory cells and may contribute to the self-limiting nature of the attacks.
- FMF is characterized by autoinflammation involving specific peripheral cells.
- Further research is needed to fully understand the significance of increased apoptosis in FMF inflammation.