0-TESTO COMPLETO.pdf - Fondazione Santa Lucia

ISS.17 – Biomarkers and diagnosis
U.O.11 – Laboratorio di Neuroimmunologia
Luca Battistini
Specific contribution of the unit to the project
For many years CD4+ T lymphocytes have taken centre stage in research
on autoimmune diseases. In more recent times, however, bolder researchers
have shown that the involvement of the immune system in the pathogenesis
of autoimmunity does not spare CD8+ lymphocytes, gd T cells, NK cells, B
lymphocytes, or dendritic cells: all these subsets have been described in the
demyelinating lesions of multiple sclerosis patients. Despite intensive
research, the triggers that determine the autoimmune attack to the central
nervous system are still unclear, although it is accepted that infectious agents
may be involved, possibly through molecular mimicry or chronic antigenic
stimulation with consequent bystander activation. However, it has been also
proposed that a host immune response targeting proteins expressed at low
levels during a latent viral infection in the CNS might underlie demyelination.
A major breakthrough in MS research has been the recent finding of EBV
persistence and reactivation in patients’ CNS. In this project we will closely
monitor immune responses to EBV in patients with relapsing-remitting, primary
progressive, or secondary progressive MS in the different phases of the
disease, in the attempt to identify biomarkers that correlate with the onset or
progression of the disease and which may be used as an aid to diagnosis and
to therapeutic efficacy. To this aim, we will use polychromatic flow cytometry
which enables the precise definition of different subsets of cells, and we will
evaluate the immune response towards EBV antigens. PBLs isolated from 140
patients with different forms of the disease will be challenged with EBV antigens
and lymphocyte responses will be measured in terms of cytokine production,
proliferation, differentiation, and cytotoxic potential. EBV-specific lymphocytes
will be detected using pentamers, and further characterized with the
aim of identifying EBV-driven biomarkers.
Finally, a growing body of evident points towards an altered function of T
regulatory (Treg) cells in autoimmune diseases and specifically in MS. Interestingly,
and relevant to this project, it is known that chronic infection can
lead to a dysregulation of T cell function. For instance, it has been suggested
that continuous stimulation of Treg cells through TLRs expressed on their
surface can inhibit the immunosuppressive function which characterizes
these cells. Thus, Treg cell phenotype, immunosuppressive function, and
response to TLR stimulation will be investigated in relation to EBV infection.
Methods
Patients. 80 RR-MS, 20 CIS, 20 PP-MS and 20 SP-MS patients and 80sex- and
age-matched healthy subjects with no previous history of neurological diseases
will be enrolled in the study. All patients will be recruited in the stable or
in the acute phase of the disease, as judged by clinical assessment, but will be
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