Modelling rheumatoid arthritis: A hybrid modelling framework to describe pannus formation in a small joint

Rheumatoid arthritis (RA) is a chronic inflammatory disorder that causes pain, swelling and stiffness in the joints, and negatively impacts the life of affected patients. The disease does not have a cure yet, as there are still many aspects of this complex disorder that are not fully understood. Whi...

Full description

Saved in:
Bibliographic Details
Main Authors: Fiona R. Macfarlane, Mark A.J. Chaplain, Raluca Eftimie
Format: Article
Language:English
Published: Elsevier 2022-06-01
Series:ImmunoInformatics
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2667119022000064
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850113577762947072
author Fiona R. Macfarlane
Mark A.J. Chaplain
Raluca Eftimie
author_facet Fiona R. Macfarlane
Mark A.J. Chaplain
Raluca Eftimie
author_sort Fiona R. Macfarlane
collection DOAJ
description Rheumatoid arthritis (RA) is a chronic inflammatory disorder that causes pain, swelling and stiffness in the joints, and negatively impacts the life of affected patients. The disease does not have a cure yet, as there are still many aspects of this complex disorder that are not fully understood. While mathematical models can shed light on some of these aspects, to date there are few such models that can be used to better understand the disease. As a first step in the mechanistic understanding of RA, in this study we introduce a new hybrid mathematical modelling framework that describes pannus formation in a small proximal interphalangeal (PIP) joint. We perform numerical simulations with this new model, to investigate the impact of different levels of immune cells (macrophages and fibroblasts) on the degradation of bone and cartilage. Since many model parameters are unknown and cannot be estimated due to a lack of experiments, we also perform a sensitivity analysis of model outputs to various model parameters (single parameters or combinations of parameters). Finally, we discuss how our model could be applied to investigate current treatments for RA, for example, methotrexate, TNF-inhibitors or tocilizumab, which can impact different model parameters.
format Article
id doaj-art-af5531dc2cb347a7aa2c259ab1b78de0
institution OA Journals
issn 2667-1190
language English
publishDate 2022-06-01
publisher Elsevier
record_format Article
series ImmunoInformatics
spelling doaj-art-af5531dc2cb347a7aa2c259ab1b78de02025-08-20T02:37:06ZengElsevierImmunoInformatics2667-11902022-06-01610001410.1016/j.immuno.2022.100014Modelling rheumatoid arthritis: A hybrid modelling framework to describe pannus formation in a small jointFiona R. Macfarlane0Mark A.J. Chaplain1Raluca Eftimie2Corresponding author.; School of Mathematics and Statistics, University of St Andrews, UKSchool of Mathematics and Statistics, University of St Andrews, UKDépartement de Mathématiques, University of Franche-Comté, Besançon, FranceRheumatoid arthritis (RA) is a chronic inflammatory disorder that causes pain, swelling and stiffness in the joints, and negatively impacts the life of affected patients. The disease does not have a cure yet, as there are still many aspects of this complex disorder that are not fully understood. While mathematical models can shed light on some of these aspects, to date there are few such models that can be used to better understand the disease. As a first step in the mechanistic understanding of RA, in this study we introduce a new hybrid mathematical modelling framework that describes pannus formation in a small proximal interphalangeal (PIP) joint. We perform numerical simulations with this new model, to investigate the impact of different levels of immune cells (macrophages and fibroblasts) on the degradation of bone and cartilage. Since many model parameters are unknown and cannot be estimated due to a lack of experiments, we also perform a sensitivity analysis of model outputs to various model parameters (single parameters or combinations of parameters). Finally, we discuss how our model could be applied to investigate current treatments for RA, for example, methotrexate, TNF-inhibitors or tocilizumab, which can impact different model parameters.http://www.sciencedirect.com/science/article/pii/S2667119022000064Rheumatoid arthritisHybrid modelStochasticityImmune response
spellingShingle Fiona R. Macfarlane
Mark A.J. Chaplain
Raluca Eftimie
Modelling rheumatoid arthritis: A hybrid modelling framework to describe pannus formation in a small joint
ImmunoInformatics
Rheumatoid arthritis
Hybrid model
Stochasticity
Immune response
title Modelling rheumatoid arthritis: A hybrid modelling framework to describe pannus formation in a small joint
title_full Modelling rheumatoid arthritis: A hybrid modelling framework to describe pannus formation in a small joint
title_fullStr Modelling rheumatoid arthritis: A hybrid modelling framework to describe pannus formation in a small joint
title_full_unstemmed Modelling rheumatoid arthritis: A hybrid modelling framework to describe pannus formation in a small joint
title_short Modelling rheumatoid arthritis: A hybrid modelling framework to describe pannus formation in a small joint
title_sort modelling rheumatoid arthritis a hybrid modelling framework to describe pannus formation in a small joint
topic Rheumatoid arthritis
Hybrid model
Stochasticity
Immune response
url http://www.sciencedirect.com/science/article/pii/S2667119022000064
work_keys_str_mv AT fionarmacfarlane modellingrheumatoidarthritisahybridmodellingframeworktodescribepannusformationinasmalljoint
AT markajchaplain modellingrheumatoidarthritisahybridmodellingframeworktodescribepannusformationinasmalljoint
AT ralucaeftimie modellingrheumatoidarthritisahybridmodellingframeworktodescribepannusformationinasmalljoint