Abstract
Alemtuzumab is a monoclonal antibody that binds to CD52, a protein present on the surface of mature lymphocytes, but not on the stem cells from which these lymphocytes are derived. It is currently used as an immune reconstitution therapy in patients with relapsing–remitting multiple sclerosis. Alemtuzumab treatment is an intermittent infusion that induces long-term remission of Multiple Sclerosis also in the treatment-free period. After the robust T and B cell depletion induced by alemtuzumab, the immune system undergoes radical changes during its reconstitution. In this review, we will discuss the current knowledge on the reconstitution of the lymphocyte repertoire after alemtuzumab treatment and how it could affect the development of side effects, which led to its temporary suspension by the European Medical Agency.
Highlights
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS) that leads to demyelination and axonal damage following the activation of both innate and adaptive immune system [1]
Alemtuzumab is a recombinant humanized immunoglobulin G1 (IgG1) monoclonal antibody directed against the CD52 surface antigen, a small (12 amino acids) glycosylphosphatidylinositol directed against the CD52 surface antigen, a small (12 amino acids) glycosylphosphatidylinositol (GPI)-anchored protein of undefined function [12]
Within 2–6 h after alemtuzumab infusion the so called “cytokine-release syndrome” was observed: The participation of monocytes, macrophages and NK cells to the lysis of lymphocytes mediated by alemtuzumab results in an acute induction of several pro-inflammatory cytokines, such as TNF-α, IL-6 and IFN-γ; the depletion of CD8+ could be associated with the increased risk of viral infection; the recovery of T cells, as results from homeostatic proliferation rather than thymic reconstitution could be associated with the development of secondary autoimmunity; the hyper population of naïve B cells could be responsible for the secondary B cell autoimmunity
Summary
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS) that leads to demyelination and axonal damage following the activation of both innate and adaptive immune system [1]. The experimental evidence coming from the murine model of MS, the Experimental Autoimmune Encephalomyelitis (EAE) and biological samples of MS patients, give us the actual comprehension of the immunological processes underlying the immunopathogenesis of MS An imbalance in both T and B cells immune regulatory network is at the basis of the autoreactive immune response and is influenced by genetics and environmental factors. Besides the adaptive immune response, microglial cells produce, in the CNS, pro-inflammatory cytokines and reactive oxygen and nitrogen species that contribute to neuroinflammation and destruction of neurons [6]. This complex cellular and molecular network that drives MS disease suggests that the preferred therapy for MS should be targeting multiple components. Its long-term efficacy and common adverse events, through an immunological point of view
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