University Hospital of Cologne
Neurology

Author Of 1 Presentation

Disease Modifying Therapies – Mechanism of Action Poster Presentation

P0287 - Alemtuzumab induces changes in the innate immune system in patients with relapsing-remitting multiple sclerosis (ID 722)

Speakers
Presentation Number
P0287
Presentation Topic
Disease Modifying Therapies – Mechanism of Action

Abstract

Background

Alemtuzumab is a humanized monoclonal antibody specific for CD52 and has been shown to be an efficient treatment for patients with relapsing-remitting multiple sclerosis (RRMS). CD52 is present at high expression levels on the surface of B- and T-lymphocytes and at low levels on monocytes and NK-cells. Recent evidence has emerged that the innate immune system might also undergo reorganization contributing to the long-lasting immunomodulatory properties of alemtuzumab.

Objectives

To better understand the effect of alemtuzumab on the innate immune system we longitudinally assessed the function of innate immune cells in a cohort of alemtuzumab treated RRMS patients. We particularly focused on distinguished monocyte and macrophage phenotypes to identify specific cellular activational patterns that are modulated during alemtuzumab treatment.

Methods

Peripheral mononuclear blood cells (PBMCs) and plasma were collected from RRMS patients before and every two months after alemtuzumab treatment for 12 months. PBMC surface marker (CD14, CD16, CD23, CD206, CD163, CD86, CCR7, HLA-DR) were assessed by flow cytometry. Monocyte function (phagocytosis of latex beads, ROS production) was examined by in vivo assays. Plasma cytokine levels were analyzed using ELISA.

Results

We observed an increase in the expression of anti-inflammatory surface markers such as CD206 and CD23 on the overall monocyte population. While the distribution of different monocyte phenotypes (classical, intermediate, and non-classical monocytes) did not change significantly after alemtuzumab treatment, several surface marker expressions within the individual phenotypes showed alterations. The CD16+ intermediate and non-classical monocytes showed an increase in anti-inflammatory CD23+, whereas the CD16- population displayed an elevation of pro-inflammatory CCR7 and CD86, 2 months post alemtuzumab treatment and a return to baseline levels later on. Furthermore, CD163+ monocytes, showing phagocytic activity were increased 6 months post-treatment and were still slightly elevated after 12 months, while phagocytosing B-cells showed an increase 12 months post alemtuzumab treatment

Conclusions

Alemtuzumab treatment goes along with complex alterations of the immune system including innate immunity mechanisms. In the peripheral blood compartment, PBMC display an increase in phagocytotic activity.

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