0-TESTO COMPLETO.pdf - Fondazione Santa Lucia

Sezione III: Attività per progetti
LIST OF PARTICIPATING UNITS
U.O.11 – Fondazione Santa Lucia, Roma – Luca Battistini
U.O.12 – Istituto Superiore di Sanità, Roma – Eliana Marina Coccia
U.O.13 – Istituto Besta, Milano – Cinthia Farina
U.O.14 – Istituto Neurologico C. Mondino, Pavia – Diego Franciotta
U.O.15 – Università di Padova – Paolo Gallo
DESCRIPTION OF THE PROJECT
What is already known on the subject
The experience and vast knowledge of the immunological dysfunctions
that underlie MS will represent the scientific platform for the re-evaluation
and definition of diagnostic parameters, based on growing evidence that supports
a key role for dysregulated EBV infection in MS pathogenesis.
The selection of novel biomarkers of disease will be performed considering
the wide heterogeneity of the cellular populations that take active part in
the immune response. For instance, we have already identified CD39
(expressed by T regulatory lymphocytes) and NKRP1A (expressed by CD8+ T
cells and by gd lymphocytes) as two molecules whose expression fluctuates
and correlates with an altered immune function during the course of MS
[Poggi et. al. (1999) J Immunol 162:4349; Borsellino et al. (2007) Blood
110:1225].
Although the involvement of activated pDC in the induction of several
autoimmune diseases has been clearly established, no data were available so
far on their role in MS pathogenesis. Recent data from groups participating to
this project indicate that activated plasmacytoid dendritic cells (pDC) accumulate
within deposits of EBV-infected cells in the MS brain [Serafini et. al.
(2007) J Exp Med 204:2899-2912; Lande et al. (in press) J Neuropathol Exp
Neurol], suggesting that the antiviral function of pDC and their secretion of
IFN-a may be critical in maintaining MS-associated immunopathology.
Infection by EBV may influence inflammation in the brain, and this can
be measured and characterized in the CSF by studying oligoclonal bands and
searching for EBV-specific immunoglobulins and other markers of a persistent
cytotoxic immune response. Immune cells in the CSF will also be investigated
with a detailed study of their phenotype and functional status. Finally,
advanced techniques of functional genomics will unveil changes in gene
expression in the blood of MS patients, which may be associated with altered
immune reactivity in the different phases of the disease.
In the last decade, there has been an intensive search for surrogate markers
of brain oxidant injury that could be used to monitor changes related to
oxidative stress as well as the efficacy of anti-oxidant therapy. Among the proposed
biomarkers are products of lipid peroxidation (e.g. 4-hydroxynonenal
and F2-isoprostanes), protein oxidation (nitrotyrosine), and DNA oxidation
(8-hydroxy-2’-deoxyguanosine, 8-OHdG). Despite lack of consensus about
638 2009