Date Published: February 8, 2018
Publisher: Public Library of Science
Author(s): Pierre de Flon, Lars Söderström, Katarina Laurell, Ann Dring, Peter Sundström, Martin Gunnarsson, Anders Svenningsson, Heinz Wiendl.
To investigate changes in the cerebrospinal fluid (CSF) immunological profile after treatment switch from first-line injectables to rituximab in patients with relapsing-remitting MS (RRMS), and to compare the profile in MS patients with healthy controls (HC).
Cerebrospinal fluid from 70 patients with clinically stable RRMS and 55 HC was analysed by a multiplex electrochemiluminescence method for a broad panel of cytokines and immunoactive substances before, and over a two-year period after, treatment switch to rituximab. After quality assessment of data, using a predefined algorithm, 14 analytes were included in the final analysis.
Ten of the 14 analytes differed significantly in MS patients compared with HC at baseline. Levels of IP-10 (CXCL10), IL-12/23p40, IL-6, sVCAM1, IL-15, sICAM1 and IL-8 (CXCL8) decreased significantly after treatment switch to rituximab. The cytokines IP-10 and IL-12/IL-23p40 displayed the largest difference versus HC at baseline and also the largest relative reduction after therapy switch to rituximab.
We found significant changes in the immunological profile after therapy switch to rituximab in RRMS in the direction towards the values of HC. IP-10 and IL12/IL-23p40 deserve further studies as part of the immunopathogenesis of MS as well as for the mode of action of rituximab in MS.
Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) where the main feature is an autoimmune attack on CNS myelin leading to damage of the myelin sheath and, if not treated adequately, a progressive loss of axons and subsequent irreversible disability [1,2]. The mechanisms inducing the inflammatory response in MS are still under intense investigation. The earlier predominant view that the inflammatory activity is mainly dependent on pro-inflammatory T-cells has been challenged by the results of treatment with B-cell depleting agents. The effect of B-cell depletion on the inflammatory activity in MS has been confirmed in several trials [3–6]. The putative biological role of B-cells in MS may be to regulate tolerance and autoimmunity through antigen-presenting characteristics and involvement in cytokine networks [7,8].
In this study, we report changes in the immunological profile of CSF from patients with clinically stable RRMS following therapy switch from first-line injectables to rituximab. The two cytokines displaying the most prominent relative changes after treatment switch to rituximab were IP-10 and IL-12/23p40. The level of these two cytokines were also the most elevated in RRMS when compared to HC, making them particularly interesting as possible mediators of a beneficial treatment effect from rituximab in MS.