Increased neutrophil apoptosis during attacks of familial Mediterranean fever.
OBJECTIVE
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).


CONCLUSIONS
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.
Ozen
S
S
Department of Pediatric Nephrology and Rheumatology, Hacettepe University Faculty of Medicine, Sihhiye 06100 Ankara, Turkey.
Uckan
D
D
Baskin
E
E
Besbas
N
N
Okur
H
H
Saatci
U
U
Bakkaloglu
A
A
D000293:Adolescent; D017209:Apoptosis / Q000502:physiology*; D001799:Blood Sedimentation; D002097:C-Reactive Protein; D002648:Child; D010505:Familial Mediterranean Fever / Q000276:immunology* / Q000503:physiopathology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000503:physiopathology; D008297:Male; D009000:Monocytes / Q000502:physiology; D009504:Neutrophils / Q000276:immunology / Q000502:physiology*; D019014:fas Receptor / Q000032:analysis / Q000378:metabolism
D019014:fas Receptor; D002097:C-Reactive Protein