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Das Spektrum der Immuntherapien bei Multipler Sklerose wird kontinuierlich erweitert. Durch die Zulassung von Cladribin und Ocrelizumab in Europa stehen aktuell zwei neue Medikamente zur Verfügung, wobei Ocrelizumab die erste Behandlungsoption für die primär progrediente Verlaufsform der Multiplen Sklerose darstellt. Mit der zunehmenden Bandbreite hochwirksamer Therapien steigt jedoch auch die Häufigkeit schwerer Nebenwirkungen. Besondere Beachtung fanden hierbei in den vergangenen Monaten die neue PML(progressive multifokale Leukenzephalopathie)-Risikoabschätzung unter Natalizumab, kardiale Nebenwirkungen unter Fingolimod, Fälle von idiopathischer thrombozytopenischer Purpura und Listerieninfektionen unter Alemtuzumab und das Auftreten von Leberversagen und Enzephalitiden unter Daclizumab. Diese Fallberichte unterstreichen die Bedeutung eines sorgfältigen Monitorings aller Patienten, die eine immunmodulatorische Therapie erhalten. [ABSTRACT FROM AUTHOR]

Background: Despite pleiotropic immunomodulatory effects of apolipoprotein E (apoE) in vitro, its effects on the clinical course of experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis (MS) are still controversial. As sex hormones modify immunomodulatory apoE functions, they may explain contentious findings. This study aimed to investigate sex-specific effects of apoE on disease course of EAE and MS.Methods: MOG(35-55) induced EAE in female and male apoE-deficient mice was assessed clinically and histopathologically. apoE expression was investigated by qPCR. The association of the MS severity score (MSSS) and APOE rs429358 and rs7412 was assessed across 3237 MS patients using linear regression analyses.Results: EAE disease course was slightly attenuated in male apoE-deficient (apoE (-/-) ) mice compared to wildtype mice (cumulative median score: apoE (-/-)  = 2 [IQR 0.0-4.5]; wildtype = 4 [IQR 1.0-5.0]; n = 10 each group, p = 0.0002). In contrast, EAE was more severe in female apoE (-/-) mice compared to wildtype mice (cumulative median score: apoE (-/-)  = 3 [IQR 2.0-4.5]; wildtype = 3 [IQR 0.0-4.0]; n = 10, p = 0.003). In wildtype animals, apoE expression during the chronic EAE phase was increased in both females and males (in comparison to naïve animals; p < 0.001). However, in MS, we did not observe a significant association between MSSS and rs429358 or rs7412, neither in the overall analyses nor upon stratification for sex.Conclusions: apoE exerts moderate sex-specific effects on EAE severity. However, the results in the apoE knock-out model are not comparable to effects of polymorphic variants in the human APOE gene, thus pinpointing the challenge of translating findings from the EAE model to the human disease. [ABSTRACT FROM AUTHOR]