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Original Contributions |

Immunological Markers of Optimal Response to Natalizumab in Multiple Sclerosis

Luisa M. Villar, PhD; María I. García-Sánchez, PhD; Lucienne Costa-Frossard, MD; Mercedes Espiño, PhD; Ernesto Roldán, PhD; Dolores Páramo, MD; Miguel Lucas, PhD; Guillermo Izquierdo, MD; José C. Álvarez-Cermeño, MD
Arch Neurol. 2012;69(2):191-197. doi:10.1001/archneurol.2011.971.
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Objective To explore cell subsets and molecules that changed specifically in patients with multiple sclerosis (MS) who had an optimal response to natalizumab. Natalizumab is a monoclonal antibody that inhibits the migration of activated immune cells to the central nervous system. It shows high efficacy in modifying the natural history of MS and induces freedom of disease activity in about 40% of treated patients with MS.

Design Prospective study of intrathecal immunoglobulin synthesis and cerebrospinal fluid lymphocyte subsets in patients with MS before and 1 year after beginning treatment with natalizumab. We monitored clinical and magnetic resonance imaging activity during a median time of 2 years.

Setting Two tertiary hospitals from the Spanish National Health Service.

Patients A total of 23 patients with MS.

Main Outcome Measures The differences between patients free of disease activity and patients with active disease during treatment.

Results Of the 23 patients, 10 (43.5%) remained free of disease activity during follow-up. The remaining 13 patients (56.5%) had relapses or new lesions despite natalizumab therapy. We did not find differences in demographic variables or clinical data between both groups prior to natalizumab therapy. All patients showed a decrease in cerebrospinal fluid CD4+ cells regardless of their response to treatment. Conversely, only patients free of disease activity showed a decrease in local IgM and, to a lesser extent, in IgG synthesis. They also showed lower percentages of B cells, particularly of CD5+ and plasmablast subsets that virtually disappeared after treatment with natalizumab.

Conclusion These data indicate that inhibition of intrathecal antibody synthesis is associated with a complete therapeutic response to natalizumab in patients with aggressive MS.

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Figure 1. IgM (A and B) and IgG oligoclonal patterns (C and D) in cerebrospinal fluid (CSF) and serum (S) samples of patients free of disease activity (A and C) or with active disease (B and D) during natalizumab treatment. Oligoclonal patterns were investigated before (BT) and 1 year after (AT) initiating natalizumab treatment.

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Figure 2. Changes in IgM (A and B) and IgG (C and D) indexes in patients with multiple sclerosis who were free of disease activity (B and D) or who had active disease (A and C) during natalizumab treatment. They were investigated before (BT) and 1 year after (AT) initiating natalizumab treatment.

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