Natalizumab exerts a suppressive effect on surrogates of B cell function in blood and CSF

• Published in: Multiple sclerosis Vol. 21; no. 8; pp. 1036 - 1044
• Main Authors: Warnke, Clemens, Stettner, Mark, Lehmensiek, Vera, Dehmel, Thomas, Mausberg, Anne K, von Geldern, Gloria, Gold, Ralf, Kümpfel, Tania, Hohlfeld, Reinhard, Mäurer, Mathias, Stangel, Martin, Straeten, Vera, Limmroth, Volker, Weber, Thomas, Kleinschnitz, Christoph, Wattjes, Mike P, Svenningsson, Anders, Olsson, Tomas, Hartung, Hans-Peter, Hermsen, Derik, Tumani, Hayrettin, Adams, Ortwin, Kieseier, Bernd C
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.07.2015; Sage Publications Ltd
• Subjects: Adult; Aged; Antigens, CD19 - blood; Antigens, CD19 - cerebrospinal fluid; B-Lymphocytes - drug effects; B-Lymphocytes - immunology; CD4-CD8 Ratio; Female; Humans; Immunoglobulin G - blood; Immunoglobulin G - cerebrospinal fluid; Immunoglobulin M - blood; Immunoglobulin M - cerebrospinal fluid; Immunologic Factors - adverse effects; Immunologic Factors - therapeutic use; Immunosuppression; JC virus; Male; Medicin och hälsovetenskap; Middle Aged; multiple sclerosis; Multiple Sclerosis - blood; Multiple Sclerosis - cerebrospinal fluid; Multiple Sclerosis - immunology; natalizumab; Natalizumab - adverse effects; Natalizumab - therapeutic use; Oligoclonal Bands - immunology; Progressive multifocal leukoencephalopathy; sease-modifying therapies; Tysabri; Young Adult; Tysabri; disease-modifying therapies; JC virus; multiple sclerosis; immunosuppression; natalizumab; Progressive multifocal leukoencephalopathy
• ISSN: 1352-4585; 1477-0970; 1477-0970
• DOI: 10.1177/1352458514556296

Background: Natalizumab for multiple sclerosis (MS) increases the risk of progressive multifocal leukoencephalopathy (PML). Objective: We aimed to assess the effect of natalizumab on cellular composition and functional B cell parameters including patients with natalizumab-associated PML (n=37). Methods: Cellular composition by flow cytometry, levels of immunoglobulin (Ig)G/IgM by immunonephelometry, and oligoclonal bands by isoelectric focusing were studied in blood and cerebrospinal fluid. Results: In MS patients treated with natalizumab without PML (n=59) the proportion of CD19+ B cells was higher in blood, but lower in cerebrospinal fluid compared with MS patients not treated with natalizumab (n=17). The CD4/CD8-ratio in cerebrospinal fluid was lower, and IgG and IgM levels as well as the IgG index dropped in longitudinal samples during natalizumab therapy. Oligoclonal bands persisted, but the total amount of the intrathecally produced IgG fraction, and the polyclonal intrathecal IgG reactivity to measles, rubella, and zoster declined. At the time of diagnosis of PML patients with natalizumab-associated PML had low total IgG levels in blood and cerebrospinal fluid. Conclusions: Natalizumab impacts B and T cell distribution and exerts an inhibitory effect on surrogates of B cell function in periphery and in cerebrospinal fluid, potentially contributing to the increased risk of developing PML.