0-TESTO COMPLETO.pdf - Fondazione Santa Lucia

ISS.17 – Biomarkers and diagnosis
which markers can be reliably used in clinical and epidemiological studies,
F2-isoprostanes have been recently recognized as the most sensitive and reliable
marker for oxidative stress. The measurement of total anti-oxidant capacity
is therefore an alternative way of investigating oxidative stress in the
course of disease.
What the project adds to the information already available
Recent evidence has indicated that the EBV virus may be involved in MS
pathogenesis. However, the cellular types involved in the immune response
against EBV and the possible correlations between viral reactivation (or, more
in general, chronic infection) and disease course have not been investigated
yet. How virus-specific T cells, T regulatory cells, and a subset of dendritic
cells which produce anti-viral interferons interact, and how these interactions
influence autoimmunity is central to the understanding of MS pathogenesis.
Finally, the identification of biomarkers correlating EBV infection, antiviral
immune response, and CNS autoimmunity should help monitor patients
avoiding expensive and time-consuming radiological examinations.
MILESTONES ALONGSIDE THE PROJECT
MI 1: Identification of new biomarkers of MS in the context of a pathogenetic
model of disease which considers an inappropriate immune response
to infection by EBV critical for disease induction.
MI 2: Identification of phenotypic and functional alterations of leukocyte
populations involved in EBV-induced inflammation.
MI 3: Knowledge on the cytotoxic factors responsible for damage to the
CNS.
MI 4: Characterization of biochemical parameters indicative of oxidative
stress.
MI 5: Correlation of MS clinical parameters with the frequency and activation
state of EBV-specific lymphocyte populations.
MI 6: Translation of the knowledge acquired on the molecular alterations
in the signalling pathways of Toll-like receptors and in the IFN-signature in
response to EBV infection to investigations in MS patients for diagnostic and
prognostic applications.
MI 7: Analysis of oligoclonal bands (total and EBV-specific) and immune
response molecules in the CSF of MS patients.
MI 8: Gene expression profiling of cells of the immune system with highthroughput
screening methodologies in CIS and distinct MS clinical courses
versus a control population. Bioinformatics analysis of such profiles.
MI 9: Validation of the differentially expressed genes by other platforms
(molecular and cellular biology).
MI10: Validation of the obtained biomarkers in the clinical follow-up of a
new cohort of MS patients.
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