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Increased procoagulant response of monocytes from patients with familial Mediterranean fever
Abstract:
Familial Mediterranean Fever (FMF) is an inherited disease of unknown etiology characterized by recurrent inflammatory episodes. Circulating fibrin was found in patients with FMF in absence of clinical manifestation of thrombosis and was statistically less frequently observed in patients treated with colchicine. These results suggest a cellular dysfunction. Therefore, we examined the procoagulant activity (PCA) of isolated mononuclear leukocytes and purified monocytes from FMF patients (n = 20). No PCA was detectable on freshly-isolated monocytes. After several hours of culture. FMF monocytes contained more PCA than control cells and the difference was more marked after endotoxin stimulation. Data obtained with coagulation factor-deficient plasma and anti-human apoprotein III antiserum indicated that the enhanced PCA in FMF monocytes is thromboplastin-like. Lysozyme and interleukin 1 production by monocytes were similar in patients and controls. The increased monocyte PCA appears to be due to an intrinsic and selective higher responsiveness of monocytes.
Insights
Familial Mediterranean Fever (FMF) patients show increased monocyte procoagulant activity (PCA) linked to cellular dysfunction. Colchicine treatment may reduce this activity, suggesting a therapeutic target for FMF.
Area of Science:
- Hematology
- Immunology
- Genetics
Background:
- Familial Mediterranean Fever (FMF) is an inherited autoinflammatory disorder characterized by recurrent inflammatory attacks.
- Circulating fibrin, indicative of clotting, is observed in FMF patients even without thrombosis, suggesting underlying cellular abnormalities.
- Colchicine treatment, a common therapy for FMF, appears to reduce circulating fibrin levels.
Purpose of the Study:
- To investigate the procoagulant activity (PCA) of monocytes in patients with Familial Mediterranean Fever (FMF).
- To determine if enhanced PCA in FMF monocytes is linked to cellular dysfunction and thromboplastin-like activity.
- To explore the potential impact of colchicine on monocyte PCA in FMF.
Main Methods:
- Isolated mononuclear leukocytes and purified monocytes from 20 FMF patients and controls were cultured.
- Procoagulant activity (PCA) was measured in monocytes after culture and endotoxin stimulation.
- Coagulation factor-deficient plasma and specific antisera were used to characterize the PCA.
Main Results:
- Freshly isolated monocytes showed no detectable PCA.
- Cultured FMF monocytes exhibited significantly higher PCA than control cells, especially after endotoxin stimulation.
- Characterization indicated the enhanced PCA in FMF monocytes is thromboplastin-like, distinct from lysozyme or interleukin-1 production.
Conclusions:
- Monocytes from FMF patients display an intrinsic, selective hyper-responsiveness leading to increased PCA.
- This enhanced monocyte PCA may contribute to the prothrombotic state observed in FMF.
- Targeting monocyte PCA could be a potential therapeutic strategy for managing FMF complications.