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CD19 as a molecular target in CNS autoimmunity

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Abstract

Multiple sclerosis (MS) and neuromyelitis optica (NMO) are the most prevalent neuroinflammatory diseases of the central nervous system (CNS). The immunological cascade of these disorders is complex, and the exact spatial and temporal role of different immune cells is not fully understood. Although MS has been considered for many years to be primarily T cell driven, it is well established that B cells and the humoral immune response play an important role in its pathogenesis. This has long been evident from laboratory findings that include the presence of oligoclonal bands in the CSF. In NMO, the importance of the humoral immune system appears even more obvious as evidenced by pathogenic antibodies against aquaporin 4 (AQP4). Besides their capacity to mature into antibody-producing plasma cells, B cells are potent antigen-presenting cells to T lymphocytes and they can provide soluble factors for cell activation and differentiation to other immune-competent cells. In MS and NMO, there are substantial data from clinical trials that B cell depletion with CD20-directed agents is effective and relatively safe. Plasma cells, which produce antibodies against molecular targets expressed by the host, but which also provide humoral immune responses against pathogens, are not targeted by anti-CD20 therapies. Therefore, the depletion of CD19-expressing cells would offer potential advantages with regard to efficacy, but potentially higher risks with regard to infectious complications. This review will outline the rationale for CD19 as a molecular target in CNS autoimmunity. The current stage of drug development is illustrated. Potential safety concerns will be discussed.

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Authors and Affiliations

  1. Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, USA

    Olaf Stüve & Krystin Deason

  2. Neurology Section, Medical Service, VA North Texas Health Care System, 4500 South Lancaster Rd, Dallas, TX, 75216, USA

    Olaf Stüve

  3. Department of Neurology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany

    Olaf Stüve

  4. Department of Neurology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany

    Clemens Warnke, Bernd C. Kieseier, Hans-Peter Hartung & Volker Knappertz

  5. Department of Neurology, Clinical Neuroimmunology and Neurochemistry, Hannover Medical School, Hannover, Germany

    Martin Stangel

  6. Department of Neurology, University of California, San Francisco, USA

    Hans-Christian von Büdingen

  7. Department of Neuroscience, Tor Vergata University and Hospital, Rome, Italy

    Diego Centonze

  8. Department of Biology, University of Texas at San Antonio, San Antonio, USA

    Thomas G. Forsthuber

  9. Teva Pharmaceuticals, Kansas City, MO, USA

    Volker Knappertz

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  1. Olaf Stüve
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Stüve, O., Warnke, C., Deason, K. et al. CD19 as a molecular target in CNS autoimmunity. Acta Neuropathol 128, 177–190 (2014). https://doi.org/10.1007/s00401-014-1313-z

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  • DOI: https://doi.org/10.1007/s00401-014-1313-z

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