title: Immune mechanisms of new therapeutic strategies in multiple sclerosis-A focus on alemtuzumab.
abstract: Alemtuzumab is a humanized monoclonal antibody targeting CD52, a broadly expressed cell surface molecule on immune cells. Application results in a rapid and long-lasting removal of lymphocyte populations from the circulation. Alemtuzumab-treatment of MS patients with relapsing-remitting forms of the disease significantly reduced the risk of relapse and accumulation of disability compared to interferon β-1a treatment in a phase II trial. Interestingly, further analysis together with parallel experimental studies suggested that alemtuzumab not only reduces disease activity due to its immune cell-depleting effect, but also confers neuroprotective effects, presumably by inducing production of neurotrophic factors in autoreactive T cells. However, alemtuzumab-treated MS patients experienced increased rates of novel autoimmunity and a slight increase in infections, demonstrating that alemtuzumab-mediated skewing of the immune cell compartment has a broad influence on immune functions. This review discusses the current concepts about the underlying mechanisms causing these altered immune responses in alemtuzumab-treated MS patients.
authors.affiliation: University of Muenster, Clinic for Neurology—Inflammatory disorders of the central nervous system and neurooncology, Muenster, Germany.
authors.forename: Luisa
authors.initials: L
authors.lastname: Klotz
authors.forename: Sven G
authors.initials: SG
authors.lastname: Meuth
authors.forename: Heinz
authors.initials: H
authors.lastname: Wiendl
mesh_terms: D000074323:Alemtuzumab; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000276:immunology / Q000494:pharmacology*; D000912:Antibodies, Neoplasm / Q000276:immunology / Q000494:pharmacology*; D002986:Clinical Trials as Topic; D006801:Humans; D007166:Immunosuppressive Agents / Q000276:immunology / Q000494:pharmacology*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000276:immunology
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D007166:Immunosuppressive Agents; D000074323:Alemtuzumab