title: A minimal unified model of disease trajectories captures hallmarks of multiple sclerosis.
abstract: Multiple Sclerosis (MS) is an autoimmune disease targeting the central nervous system (CNS) causing demyelination and neurodegeneration leading to accumulation of neurological disability. Here we present a minimal, computational model involving the immune system and CNS that generates the principal subtypes of the disease observed in patients. The model captures several key features of MS, especially those that distinguish the chronic progressive phase from that of the relapse-remitting. In addition, a rare subtype of the disease, progressive relapsing MS naturally emerges from the model. The model posits the existence of two key thresholds, one in the immune system and the other in the CNS, that separate dynamically distinct behavior of the model. Exploring the two-dimensional space of these thresholds, we obtain multiple phases of disease evolution and these shows greater variation than the clinical classification of MS, thus capturing the heterogeneity that is manifested in patients.
authors.affiliation: Unit of Computational Medicine, Center for Molecular Medicine, Department of Medicine, Solna, Karolinska Institutet 17176, Sweden.
authors.forename: Venkateshan
authors.initials: V
authors.lastname: Kannan
authors.affiliation: Unit of Computational Medicine, Center for Molecular Medicine, Department of Medicine, Solna, Karolinska Institutet 17176, Sweden.
authors.forename: Narsis A
authors.initials: NA
authors.lastname: Kiani
authors.affiliation: Unit of NeuroImmunology, Center for Molecular Medicine, Department of Clinical Neuroscience, Karolinska University Hospital L8 17176, Stockholm, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Piehl
authors.affiliation: Unit of Computational Medicine, Center for Molecular Medicine, Department of Medicine, Solna, Karolinska Institutet 17176, Sweden; Biological and Environmental Sciences and Engineering Division, Computer, Electrical and Mathematical Sciences and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia. Electronic address: jesper.tegner@ki.se.
authors.forename: Jesper
authors.initials: J
authors.lastname: Tegner
mesh_terms: D002490:Central Nervous System / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D003198:Computer Simulation; D006801:Humans; D009103:Multiple Sclerosis / Q000145:classification / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology*; D020528:Multiple Sclerosis, Chronic Progressive / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000276:immunology / Q000473:pathology / Q000503:physiopathology