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Circulating myeloid suppressor cells as a translational tool for biomarker discovery in multiple sclerosis

Diego Clemente

National Hospital of Paraplegics & CIBERNED (Toledo, Spain)

15 May 2023 13:00

Aketxe Room, Sede Building, Leioa

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One of the main characteristics of multiple sclerosis (MS) is the great variability of symptoms and the unpredictability of its disease course. The growing number of treatments available for MS highlights the importance of finding biomarkers to help clinicians make the right therapeutic decisions early in the disease.

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of immature cells with a crucial role in regulating the immune response in MS. Monocytic-MDSCs (M-MDSCs) have been studied in the peripheral blood of MS patients with controversial results: some authors described a little variation of M-MDSCs during the clinical course, while others observed its increase at relapses. Notably, the function of M-MDSCs in MS is also a matter of debate, as they exhibit a suppressive activity in relapsing-remitting MS (RRMS), which is lost or opposite in progressive patients. Despite these results from the peripheral blood, there are no data about their presence/origin in the CNS of MS patients or about the relationship between these regulatory cells and the MS clinical severity.

Fingolimod (FTY720) is an oral disease modifying treatment approved for relapsing-remitting MS. It acts as a sphingosine-1-phosphate receptor modulator preventing lymphocyte egress from lymphoid tissues. Fingolimod promotes the immunosuppressive activity of MDSCs in different experimental models of autoimmune diseases. However, the relation between fingolimod and MDSCs in the context of MS remains elusive.

In the present work, I will summarize the last data from our lab describing the following aspects: 1) M-MDSC presence, characterization and distribution in the brain of MS patients, 2) the relationship of M-MDSC density and the previous disease severity, 3) translation of these data into the search for biomarkers to predict disease severity, recovery from relapses and response to disease-modifying treatments (e.g. fingolimod).

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