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  • 1.
    Carlström, Karl E.
    et al.
    Department of Clinical Neurosciences, Section of Neurology, Karolinska Institutet, Stockholm, Sweden.
    Ewing, Ewoud
    Department of Clinical Neurosciences, Section of Neurology, Karolinska Institutet, Stockholm, Sweden.
    Granqvist, Mathias
    Department of Clinical Neurosciences, Section of Neurology, Karolinska Institutet, Stockholm, Sweden.
    Gyllenberg, Alexandra
    Department of Clinical Neurosciences, Section of Neurology, Karolinska Institutet, Stockholm, Sweden.
    Aeinehband, Shahin
    Department of Clinical Neurosciences, Section of Neurology, Karolinska Institutet, Stockholm, Sweden.
    Enoksson, Sara Lind
    Department of Clinical Immunology Karolinska University Hospital, Stockholm, Sweden.
    Checa, Antonio
    Division of Physiological Chemistry II, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
    Badam, Tejaswi
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Department of Physics, Chemistry & Biology (IFM), Bioinformatics, Linköping University, Sweden.
    Huang, Jesse
    Department of Clinical Neurosciences, Section of Neurology, Karolinska Institutet, Stockholm, Sweden.
    Gomez-Cabrero, David
    Translational Bioinformatics Unit, Navarrabiomed, Complejo Hospitalario de Navarra (CHN), Universidad Publica de Nevarra (UPNA), IdiSNA, Pamplona, Spain.
    Gustafsson, Mika
    Department of Physics, Chemistry and Biology, Linköping University, Sweden.
    Al Nimer, Faiez
    Department of Clinical Neurosciences, Section of Neurology, Karolinska Institutet, Stockholm, Sweden.
    Wheelock, Craig E.
    Division of Physiological Chemistry II, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
    Kockum, Ingrid
    Department of Clinical Neurosciences, Section of Neurology, Karolinska Institutet, Stockholm, Sweden.
    Olsson, Tomas
    Department of Clinical Neurosciences, Section of Neurology, Karolinska Institutet, Stockholm, Sweden.
    Jagodic, Maja
    Department of Clinical Neurosciences, Section of Neurology, Karolinska Institutet, Stockholm, Sweden.
    Piehl, Fredrik
    Department of Clinical Neurosciences, Section of Neurology, Karolinska Institutet, Stockholm, Sweden.
    Therapeutic efficacy of dimethyl fumarate in relapsing-remitting multiple sclerosis associates with ROS pathway in monocytes2019In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 10, no 1, p. 1-13, article id 3081Article in journal (Refereed)
    Abstract [en]

    Dimethyl fumarate (DMF) is a first-line-treatment for relapsing-remitting multiple sclerosis (RRMS). The redox master regulator Nrf2, essential for redox balance, is a target of DMF, but its precise therapeutic mechanisms of action remain elusive. Here we show impact of DMF on circulating monocytes and T cells in a prospective longitudinal RRMS patient cohort. DMF increases the level of oxidized isoprostanes in peripheral blood. Other observed changes, including methylome and transcriptome profiles, occur in monocytes prior to T cells. Importantly, monocyte counts and monocytic ROS increase following DMF and distinguish patients with beneficial treatment-response from non-responders. A single nucleotide polymorphism in the ROS-generating NOX3 gene is associated with beneficial DMF treatment-response. Our data implicate monocyte-derived oxidative processes in autoimmune diseases and their treatment, and identify NOX3 genetic variant, monocyte counts and redox state as parameters potentially useful to inform clinical decisions on DMF therapy of RRMS.

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