Effects of ocrelizumab on NK cell activation in Relapsing Multiple Sclerosis
Gianmarco Abbadessa1, Sara Bruzzaniti2, Giuseppina Miele1, Erica Piemonte2, Maria Teresa Lepore2, Elisabetta Signoriello1, Giacomo Lus1, Giuseppe Matarese2, Mario Galgani2, Simona Bonavita1
1University of Campania Luigi Vanvitelli, 2University of Naples Federico II
Objective:

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. 

Background:

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.

Design/Methods:

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.

Results:

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.

Conclusions:
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.
10.1212/WNL.0000000000203069