Experimental Neuromyelitis Optica Induces a Type I Interferon Signature in the Spinal Cord.
نویسندگان
چکیده
Neuromyelitis optica (NMO) is an acute inflammatory disease of the central nervous system (CNS) which predominantly affects spinal cord and optic nerves. Most patients harbor pathogenic autoantibodies, the so-called NMO-IgGs, which are directed against the water channel aquaporin 4 (AQP4) on astrocytes. When these antibodies gain access to the CNS, they mediate astrocyte destruction by complement-dependent and by antibody-dependent cellular cytotoxicity. In contrast to multiple sclerosis (MS) patients who benefit from therapies involving type I interferons (I-IFN), NMO patients typically do not profit from such treatments. How is I-IFN involved in NMO pathogenesis? To address this question, we made gene expression profiles of spinal cords from Lewis rat models of experimental neuromyelitis optica (ENMO) and experimental autoimmune encephalomyelitis (EAE). We found an upregulation of I-IFN signature genes in EAE spinal cords, and a further upregulation of these genes in ENMO. To learn whether the local I-IFN signature is harmful or beneficial, we induced ENMO by transfer of CNS antigen-specific T cells and NMO-IgG, and treated the animals with I-IFN at the very onset of clinical symptoms, when the blood-brain barrier was open. With this treatment regimen, we could amplify possible effects of the I-IFN induced genes on the transmigration of infiltrating cells through the blood brain barrier, and on lesion formation and expansion, but could avoid effects of I-IFN on the differentiation of pathogenic T and B cells in the lymph nodes. We observed that I-IFN treated ENMO rats had spinal cord lesions with fewer T cells, macrophages/activated microglia and activated neutrophils, and less astrocyte damage than their vehicle treated counterparts, suggesting beneficial effects of I-IFN.
منابع مشابه
Author's response to reviews Title:Comparative clinical characteristics of neuromyelitis optica spectrum disorders with and without spinal cord atrophy Authors:
متن کامل
Poor Responses to Interferon-Beta Treatment in Patients with Neuromyelitis Optica and Multiple Sclerosis with Long Spinal Cord Lesions
Interferon-beta (IFN-β) treatment may not be effective in neuromyelitis optica (NMO). Whether the poor response to IFN-β is related to long spinal cord lesions (LSCL) or the NMO disease entity itself is unclear. We evaluated the spinal cord involvement of patients with multiple sclerosis (MS) and NMO, as well as the response after receiving IFN-β. Forty-nine MS and 21 NMO patients treated with ...
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Typical NMO is characterized by simultaneous or sequential acute transverse myelitis and optic neuritis. Spinal cord lesions extending over 3 or more vertebral segments and normal brain imaging are the typical MRI findings in NMO. In typical cases with positive NMO antibody the diagnosis is easy but in seronegative and atypical cases with different clinical manifestations and MRI features the d...
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OBJECTIVE Neuromyelitis optica (NMO) is characterized by selective inflammation of the spinal cord and optic nerves but is distinct from multiple sclerosis (MS). Interferon (IFN)-β mitigates disease activity in MS, but is controversial in NMO, with a few reports of disease worsening after IFN-β therapy in this highly active disease. In systemic lupus erythematosus (SLE), IFNs adversely affect d...
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ورودعنوان ژورنال:
- PloS one
دوره 11 3 شماره
صفحات -
تاریخ انتشار 2016