Impact of Cerebrospinal Fluid Oligoclonal Bands Disappearance in Patients with Multiple Sclerosis treated with Natalizumab: evaluation of clinical, radiological and immunological aspects associated with JC virus infection stratification.

• Grant number: 13/00550-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: June 01, 2013
• End date: May 31, 2016
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Leonilda Maria Barbosa dos Santos
• Grantee: Felipe von Glehn Silva
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated scholarship(s): 13/11959-7 - Understanding the role of antigen presenting cells in MS patients and the impact of the different treatments over the innate immunity, BE.EP.PD

Abstract

In the last years, several effective medications were introduced on the market, called disease modifying therapies, e.g. recombinant interferon ² (INF-²) and glatiramer acetate (GA), but they have a partial control on multiple sclerosis (MS). In 2006, a monoclonal humanized antibody (Natalizumab) that binds to ±4 subunit of integrins expressed on activated T cells surface showed a superior efficacy compared to the existing therapies. However, this treatment is associated with a serious side effect, which is the risk of development of progressive multifocal leukoencephalopathy (PML) caused by the JC virus.Natalizumab hinders the migration of T auto-reactive cells across the blood brain barrier to CNS, reducing inflammatory response. Recently, we described the disappearance of cerebrospinal fluid IgG oligoclonal bands (CSF OCB) of natalizumab treated patients. This is interesting because CSF OCB persists during disease clinical course and no existing treatment demonstrated to interfere with its production. We do not know yet the clinical implication of this BOC disappearance, but it may be linked to a down regulation of the inflammatory response or to an increased risk to CNS JC virus infection. This study aim to determine the frequency of CSF OCB disappearance in the natalizumab treated group, to determine if there are differences longitudinally in the clinical and radiological course between these two groups, to determine if the disappearance of CSF OCB is linked to risks to develop CNS JC virus infection and to characterize the B lymphocytes in the context of MS pathogenesis.