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Unified Modeling of Familial Mediterranean Fever and Cryopyrin Associated Periodic Syndromes.

Bozkurt Y, Demir A, Erman B, Gül A - Comput Math Methods Med (2015)

Bottom Line: One of the subsystems, which contains a coupled positive-negative feedback motif, captures the dynamics of inflammation formation and regulation.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.

View Article: PubMed Central - PubMed

Affiliation: Computational and Quantitative Biology Lab, Koc University, 34450 Istanbul, Turkey.

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.

No MeSH data available.


Related in: MedlinePlus

R levels in Healthy, FMF, and CAPS cases.
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fig11: R levels in Healthy, FMF, and CAPS cases.

Mentions: We now present time-domain simulations for R, I, A, PC, and C in response to a pulse trigger input in Healthy and FMF modes and a constant trigger in CAPS, as shown in Figures 11, 12, 13, 14, and 15. In Healthy and FMF modes, magnitude of T is stepped from 0.1 to 0.94 and back to 0.1. The trigger is applied at time = 100 and duration of the trigger pulse is set to 150. In CAPS, a constant base trigger level of T = 0.1 is applied. The dashed lines represent T in the plots.


Unified Modeling of Familial Mediterranean Fever and Cryopyrin Associated Periodic Syndromes.

Bozkurt Y, Demir A, Erman B, Gül A - Comput Math Methods Med (2015)

R levels in Healthy, FMF, and CAPS cases.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4464681&req=5

fig11: R levels in Healthy, FMF, and CAPS cases.
Mentions: We now present time-domain simulations for R, I, A, PC, and C in response to a pulse trigger input in Healthy and FMF modes and a constant trigger in CAPS, as shown in Figures 11, 12, 13, 14, and 15. In Healthy and FMF modes, magnitude of T is stepped from 0.1 to 0.94 and back to 0.1. The trigger is applied at time = 100 and duration of the trigger pulse is set to 150. In CAPS, a constant base trigger level of T = 0.1 is applied. The dashed lines represent T in the plots.

Bottom Line: One of the subsystems, which contains a coupled positive-negative feedback motif, captures the dynamics of inflammation formation and regulation.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.

View Article: PubMed Central - PubMed

Affiliation: Computational and Quantitative Biology Lab, Koc University, 34450 Istanbul, Turkey.

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.

No MeSH data available.


Related in: MedlinePlus