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Abstract Details

Effects of ocrelizumab on NK cell activation in Relapsing Multiple Sclerosis
Multiple Sclerosis
P6 - Poster Session 6 (5:30 PM-6:30 PM)
3-004

Ocrelizumab, a humanized monoclonal anti-CD20 antibody, has shown pronounced effects in reduction of disease activity in RMS. Although the clinical response to ocrelizumab is related to a specific B cell depletion, other circulating lymphocytes may be affected by this treatment.

Concerning NK lymphocytes, several studies have shown potential regulatory properties of these cells in MS. Some activator cytotoxicity receptors (CD94/NKG2C, NKG2D, NKp46, and DNAM) were suggested to mediate NK cytotoxic regulatory function. Anti-CD20 agents showed to drive the selective in vitro expansion of CD94/NKG2C+ memory NK cells and to enhance their cytotoxic function. However, the phenotypic changes induced by ocrelizumab on NK cell subsets in vivo and their pathogenetic implication are still unexplored.

To evaluate the effects of ocrelizumab on circulating immune asset in Relapsing Multiple Sclerosis (RMS) subjects, with a specific focus on NK cell activation profile. 

In this prospective longitudinal study, we enrolled 30 RMS patients. RMS patients were treated with ocrelizumab and followed up for twelve months. Frequency and phenotype of several circulating T cell subsets as well as NK cell phenotypic profile were evaluated by flow cytometry, before and after the treatment.

Six and twelve months after the treatment, a reduction of absolute lymphocyte count was observed. We also noticed increased percentage of T cell subsets with naïve phenotype (CD4+CD45RA+ and CD8+CD45RA+ cells). In parallel, a reduction of activated/memory T cell percentage was observed (CD4+CD45RO+ and CD8+CD45RO+ cells). Further, flow cytometry phenotypic analysis revealed an increased proportion of NK cells expressing the activating receptors, CD94/NKG2C, NKG2D, NKp46 and DNAM upon ocrelizumab treatment.

Ocrelizumab affects T cell compartment, favoring reduction of activated/memory T cells in RMS patients. Further, ocrelizumab induces phenotypical changes in NK cells toward a higher cytotoxic/regulatory profile in RMS patients.

Authors/Disclosures
Gianmarco Abbadessa, MD (University of Campania Luigi Vanvitelli)
PRESENTER
Dr. Abbadessa has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck.
No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file
Elisabetta Signoriello Elisabetta Signoriello has nothing to disclose.
Giacomo Lus (Policlinico di Napoli) Giacomo Lus has nothing to disclose.
No disclosure on file
No disclosure on file
No disclosure on file