Abstract |
Familial mediterranean fever (FMF) and Cryopyrin associated periodic syndromes (CAPS) are two prototypical hereditary autoinflammatory diseases, characterized by recurrent episodes of fever and inflammation as a result of mutations in MEFV and NLRP3 genes encoding Pyrin and Cryopyrin proteins, respectively. Pyrin and Cryopyrin play key roles in the multiprotein inflammasome complex assembly, which regulates activity of an enzyme, Caspase 1, and its target cytokine, IL-1β. Overproduction of IL-1β by Caspase 1 is the main cause of episodic fever and inflammatory findings in FMF and CAPS. We present a unifying dynamical model for FMF and CAPS in the form of coupled nonlinear ordinary differential equations. The model is composed of two subsystems, which capture the interactions and dynamics of the key molecular players and the insults on the immune system. One of the subsystems, which contains a coupled positive-negative feedback motif, captures the dynamics of inflammation formation and regulation. We perform a comprehensive bifurcation analysis of the model and show that it exhibits three modes, capturing the Healthy, FMF, and CAPS cases. The mutations in Pyrin and Cryopyrin are reflected in the values of three parameters in the model. We present extensive simulation results for the model that match clinical observations.
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Authors | Yasemin Bozkurt, Alper Demir, Burak Erman, Ahmet Gül |
Journal | Computational and mathematical methods in medicine
(Comput Math Methods Med)
Vol. 2015
Pg. 893507
( 2015)
ISSN: 1748-6718 [Electronic] United States |
PMID | 26161132
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Carrier Proteins
- Cytoskeletal Proteins
- IL1B protein, human
- IL1R2 protein, human
- IL1RN protein, human
- IL6 protein, human
- Inflammasomes
- Interleukin 1 Receptor Antagonist Protein
- Interleukin-1beta
- Interleukin-6
- MEFV protein, human
- NLR Family, Pyrin Domain-Containing 3 Protein
- NLRP3 protein, human
- Pyrin
- Receptors, Interleukin-1
- Receptors, Interleukin-1 Type II
- TIR8 protein, human
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Topics |
- Algorithms
- Carrier Proteins
(genetics)
- Computer Simulation
- Cryopyrin-Associated Periodic Syndromes
(diagnosis, physiopathology)
- Cytoskeletal Proteins
(genetics)
- Familial Mediterranean Fever
(diagnosis, physiopathology)
- Humans
- Inflammasomes
- Inflammation
- Interleukin 1 Receptor Antagonist Protein
(physiology)
- Interleukin-1beta
(physiology)
- Interleukin-6
(physiology)
- Models, Biological
- Mutation
- NLR Family, Pyrin Domain-Containing 3 Protein
- Pyrin
- Receptors, Interleukin-1
(physiology)
- Receptors, Interleukin-1 Type II
(physiology)
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