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    • It therefore appears that an autoimmune reaction in CIDP may

    2018-10-23

    It therefore appears that an autoimmune reaction in CIDP may result from a TLR4-driven activation of innate immunity by MSRV-Env protein in immune and neuroglial cell types with potential downstream superantigen-like effects when T-cells are recruited and exposed to MSRV-Env (Perron et al., 2001). A mechanism of TLR-conditional activation of lymphocyte by innate immune and/or antigen presenting rsv has now been evidenced (Kool et al., 2011), which may differentiate eventual TLR-dependent superantigen effects from the direct T-cell polyclonal activation observed with bacterial superantigens (Muller-Alouf et al., 2001). In all instances, superantigenic effects cause antigen-independent polyclonal activation of T lymphocytes, which was incriminated in MS (Rudge, 1991) and was more recently experimentally evidenced with MSRV-Env induction of autoimmunity against the central nervous system myelin proteins in animal models (Perron et al., 2013). Consistent with this known pathogenic potential, MSRV-Env protein expression as observed in HSC within CIDP peripheral nerve lesions may therefore trigger inflammation along peripheral nerves mirrored by systemic immune dysregulation. Of note, MSRV-Env was not detected in similar biopsy from a control case presenting inflammatory lesions with perivascular leukocyte infiltration, which adds to the demonstration that MSRV-Env is not a consequence of inflammation, but the reverse. Finally, the present study also showed that the strong pro-inflammatory upregulation of IL6 and CXCL10 induced by MSRV-Env in HSC was significantly inhibited by a specific neutralizing antibody targeting MSRV-Env, GNbAC1. As this antibody is a humanized therapeutic IgG4, now in phase II clinical trials in MS (Curtin et al., 2015; Derfuss et al., 2015; Zimmermann et al., 2015), this indicates potential new avenues for the treatment of CIDP patients with significantly elevated MSRV expression.
    Potential Conflicts of Interest
    Authors\' Contributions
    Introduction Migraine is associated with a two-fold increased relative risk for stroke (Etminan et al., 2005; Schurks et al., 2009; Spector et al., 2010). Etiology of stroke in migraine remains still obscure (Kurth and Diener, 2012). It is not known whether it is thromboembolic or migraine-specific being different from that of thromboembolism (Kurth and Diener, 2012). Studies relate migraine to hemorrhagic stroke but they are too few and too small to make conclusions about etiology (Sacco et al., 2013; Kurth and Tzourio, 2013). The reason for our insufficient knowledge on stroke in migraineurs is in part that the increased risk in absolute terms is small and available studies on the risk for stroke among migraineurs are hampered by small numbers weakening the reliability of risk estimations (Kurth and Diener, 2012).
    Methods The study is a cohort study on all Danes aged 25–80years who lived in Denmark during some or all of the period between January 1, 2003 and December 31, 2011. The cohort was linked to the Danish registries by the unique personal identification number to obtain information on triptan use, strokes and confounders (i.e. education and disposable income). Information on hospitalization for stroke was obtained from the Danish Stroke Registry (Olsen et al., 2007; Mainz et al., 2004). Stroke was defined according to World Health Organization criteria (Report of the WHO Task Force on Stroke and other Cerebrovascular Disorders, 1989) and we included incident hospital admissions for first-ever stroke (ischemic or hemorrhagic; ICD-10 codes I61 and I63) in the period 2003–2011. For patients with multiple hospital admissions, only the first admission was included. Transient ischemic attacks were not included in the Registry. Patients aged <25 and >80years were excluded from the study, as well as patients for whom scanning was not performed (0.4%)/result not available (0.7%). Most stroke patients (90%) are admitted to hospital, as access to hospital care is free in Denmark (Jørgensen et al., 1992). Information on education and disposable income for the cohort was obtained from Statistics Denmark (Dalton et al., 2008); both variables are associated with incidence of stroke and to some level proxies for lifestyle factors such as smoking (Dalton et al., 2008). Education was grouped into three categories: basic/high school (7–12years of primary, secondary, and grammar-school education); vocational (10–12years of education including vocational training); and higher (≥13years of education) (Dalton et al., 2008). People for whom information on education was missing were excluded (14%). Disposable income was defined as household income after taxation and interest per person, adjusted for the number of people in the household and deflated according to the 2000 value of the Danish crown (DKK). For the analyses, disposable income was categorized into the 20th, 40th, 60th, and 80th percentiles of the age and gender-specific income distribution.