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Computational and Mathematical Methods in Medicine
Volume 2015, Article ID 893507, 18 pages
http://dx.doi.org/10.1155/2015/893507
Research Article

Unified Modeling of Familial Mediterranean Fever and Cryopyrin Associated Periodic Syndromes

1Computational and Quantitative Biology Lab, Koc University, 34450 Istanbul, Turkey
2Division of Rheumatology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, 34093 Istanbul, Turkey

Received 18 September 2014; Accepted 24 November 2014

Academic Editor: Francesco Camastra

Copyright © 2015 Yasemin Bozkurt et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.