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THU0232 Fas and apoptosis in patients with familial mediterranean fever and amyloidosis
  1. S Kiraz1,
  2. I Ertenli1,
  3. M Çalgüneri1,
  4. MA Oztürk1,
  5. E Atalar2,
  6. S Apras1,
  7. IC Haznedaroglu3,
  8. S Kirazlı3
  1. 1Rheumatology
  2. 2Cardiology
  3. 3Hematology, Hacettepe University School of Medicine, Ankara, Turkey

Abstract

Background Amyloidosis is the drastic complication of familial Mediterranean Fever (FMF). Amyloidosis may be characterised by a tendency for keratinocytes to undergo filamentous degeneration and apoptosis. However, a possible association of FMF and apoptosis has not been previously evaluated. Binding of Fas ligand (FasL) to the Fas antigen trigger the cytoplasmic apoptotic signal. Induced cell death can be inhibited by soluble Fas protein (sFas) which binds to and functions as competitive antagonist of FasL.

Objectives The aim of this study was to investigate sFas in patients with FMF complicated with amyloidosis compared to FMF patients without amyloidosis and controls.

Methods Ten FMF patients with amyloidosis (mean age: 41.8, min-max: 33–51), 12 patients with FMF without amyloidosis (mean age: 24.8, min-max: 17–38) and 16 controls (mean age: 48.7, min-max: 38–63) were enrolled in the study. All FMF patients were in attack-free period during blood sampling. sFas levels were measured using a commercially available ELISA kit (Quantikine sFas Immunoassay).

Conclusion Decreased serum sFas levels may lead to unbalanced binding of FasL to its receptor, inducing apoptosis. In vitro experiments demonstrated that long-term enhancement of Fas expression in Fas-normal mice resulted in an increased acute-phase response and renal amyloidosis in aged transgenic mice. Increased Fas expression in T cells of aged CD2-Fas transgenic CD-1 mice resulted in an increased immune response and T cell apoptosis. Therefore, enhanced Fas-mediated apoptosis can be associated with amyloidosis in FMF patients, and this association may be related to the dysregulated immune system activation. On the other hand, elevated levels of sFas protein in patients with FMF may also be related to the imbalanced inflammatory activity. Induced cell death of autoreactive T cells could be inhibited by sFas. sFas levels were shown to be elevated in patients with active SLE. However this observation could not be confirmed by some other authors. Since the changes in autoimmune inflammatory disorders are dynamic and complex, it is difficult to establish a relationship between sFas and their pathogenesis. It also remains to be detected which cells release the elevated amounts of sFas. Future studies are needed to elucidate exact state of sFas protein in the etiopathogenesis of FMF.

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