dc.contributor.author |
Domingo i Espinós, Júlia |
dc.date |
2013-09-30 |
dc.identifier.uri |
http://hdl.handle.net/10230/21136 |
dc.format |
application/pdf |
dc.language.iso |
eng |
dc.rights |
© Tots els drets reservats |
dc.rights |
info:eu-repo/semantics/openAccess |
dc.subject |
Esclerosi múltiple |
dc.subject |
Treball de fi de grau -- Curs 2012-2013 |
dc.title |
Neutralizing antibodies in Multiple Sclerosis a model-based analysis of Interferon beta signaling pathway in macrophages |
dc.type |
info:eu-repo/semantics/bachelorThesis |
dc.description.abstract |
Treball de fi de grau en Biologia Humana |
dc.description.abstract |
Supervisors: Jordi Garcia Ojalvo i/nElena Abad |
dc.description.abstract |
Multiple Sclerosis is the most common non-traumatic cause of neurological/ndisability in young people. There is no cure yet, and until recently, few long-term/ntherapies existed. Interferon beta (IFNβ) was the first treatment, and remains the most/ncommonly prescribed. One of the most significant problems of IFNβ therapy is the/nproduction of drug specific antibodies. Up to 45% of patients develop neutralizing/nantibodies (NAbs) to IFNβ products. The neutralizing antibody binds to the biological/nagent preventing its interaction with its receptor, inhibiting the biological action of the/nprotein, which abrogates the clinical efficacy of IFNβ treatment. Interferon-beta/nmediates its response by binding to its high affinity cell surface receptor and initiating/nthe JAK/STAT signalling cascade. In this project we have analyzed the IFNβ signaling/npathway in macrophages when neutralizing antibodies are present. The response to/nthis pathway after IFNβ stimulation shows a transient oscillatory rhythm of STAT1/nphosphorylation, which varies as NAbs concentration increases. To improve our/nunderstanding of that behavior, we extended an existing mathematical model based on/nnonlinear ordinary differential equations of JAK/STAT pathway by including IFN-NAb/nassociation and IFN-activation receptor. Combining our theoretical model with/nexperimental data we could study the role of neutralizing antibodies on the molecular/nresponse and determine its lifetime after cytokine stimulation. |