IFNβ-1b may severely exacerbate Japanese optic-spinal MS in neuromyelitis optica spectrum

Shimizu, Jun; Hatanaka, Y.; Hasegawa, Mitsuhiro; Iwata, Ayaka J.; Sugimoto, Ikuo; Date, Hiroaki; Goto, J; Shimizu, Takahiro; Takatsu, Masami; Sakurai, Yasuhisa; Nakase, Hiroyuki; Uesaka, Yoshikazu; Hashida, Hideji; Hashimoto, Koji; Komiya, Tatsuhiko; Tsuji, Sadatoshi

doi:10.1212/wnl.0b013e3181f8832e

Cited by 178 publications

(118 citation statements)

References 25 publications

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“…Consistent with our findings, IFN-b administration was reported to exacerbate EAE that was induced by adoptively transferring Th17 cells (24). In addition, NMO patients, who are thought to have greater Th17 pathology than MS patients, have been shown to deteriorate after receiving IFN-b therapy (46,47). More notably, consistent with an inhibitory role of Sema4A in IL-10 production (35), we found that patients with high serum Sema4A levels had low serum IL-10 levels.…”

Section: Discussionsupporting

confidence: 86%

Elevation of Sema4A Implicates Th Cell Skewing and the Efficacy of IFN-β Therapy in Multiple Sclerosis

Nakatsuji

Okuno

Moriya

et al. 2012

The Journal of Immunology

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Multiple sclerosis (MS) is a demyelinating autoimmune disease of the CNS and a leading cause of lasting neurologic disabilities in young adults. Although the precise mechanism remains incompletely understood, Ag presentation and subsequent myelin-reactive CD4+ T cell activation/differentiation are essential for the pathogenesis of MS. Although semaphorins were initially identified as axon guidance cues during neural development, several semaphorins are crucially involved in various phases of immune responses. Sema4A is one of the membrane-type class IV semaphorins, which we originally identified from the cDNA library of dendritic cell (DC). Sema4A plays critical roles in T cell activation and Th1 differentiation during the course of experimental autoimmune encephalomyelitis, an animal model of MS; however, its pathological involvement in human MS has not been determined. In this study, we report that Sema4A is increased in the sera of patients with MS. The expression of Sema4A is increased on DCs in MS patients and shed from these cells in a metalloproteinase-dependent manner. DC-derived Sema4A is not only critical for Th1 but also for Th17 cell differentiation, and MS patients with high Sema4A levels exhibit Th17 skewing. Furthermore, patients with high Sema4A levels have more severe disabilities and are unresponsive to IFN-β treatment. Taken together, our results suggest that Sema4A is involved in the pathogenesis of MS by promoting Th17 skewing.

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Section: Discussionsupporting

confidence: 86%

Elevation of Sema4A Implicates Th Cell Skewing and the Efficacy of IFN-β Therapy in Multiple Sclerosis

Nakatsuji

Okuno

Moriya

et al. 2012

The Journal of Immunology

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“…This distinction has critical therapeutic implications: NMO does not respond to traditional MS immunomodulatory therapy with ␤-interferon, which in some patients may even be deleterious. 13,14 Similarly, severe exacerbations of NMO have been reported in patients treated with natalizumab, 5 an efficacious monoclonal antibody therapy for MS. Case series do suggest that NMO responds to immunosuppressive therapy and, in particular, to the B-cell-depleting anti-CD20 monoclonal antibody, rituximab. 77 Of relevance to the neuroradiologist, rituximab has been associated with progressive multifocal leukoencephalopathy in patients with systemic autoimmune disease, 78 and heightened vigilance for this complication in patients with NMO is paramount.…”

Section: Discussionmentioning

confidence: 96%

“…Neuroimaging has an increasingly important role in both the diagnosis and management of this potentially devastating condition. First, timely differentiation of NMO from MS is critical and the motivator for this review: Early and aggressive immunosuppression is required to prevent or reduce potentially severe disability in NMO, whereas the application of MS-specific therapies can exacerbate the disease 13,14 or even precipitate severe atypical relapses. 5,15 Second, serial imaging has an important role in disease monitoring and informs understanding of the temporal aspects of NMO pathophysiology.…”

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confidence: 99%

Conventional and Advanced Imaging in Neuromyelitis Optica

Barnett

Sutton

Ghadiri

et al. 2013

American Journal of Neuroradiology

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SUMMARY:Myelitis and optic neuritis are prototypic clinical presentations of both multiple sclerosis and neuromyelitis optica. Once considered a subtype of multiple sclerosis, neuromyelitis optica, is now known to have a discrete pathogenesis in which antibodies to the water channel, aquaporin 4, play a critical role. Timely differentiation of neuromyelitis optica from MS is imperative, determining both prognosis and treatment strategy. Early, aggressive immunosuppression is required to prevent the accrual of severe disability in neuromyelitis optica; conversely, MS-specific therapies may exacerbate the disease. The diagnosis of neuromyelitis optica requires the integration of clinical, MR imaging, and laboratory data, but current criteria are insensitive and exclude patients with limited clinical syndromes. Failure to recognize the expanding spectrum of cerebral MR imaging patterns associated with aquaporin 4 antibody seropositivity adds to diagnostic uncertainty in some patients. We present the state of the art in conventional and nonconventional MR imaging in neuromyelitis optica and review the place of neuroimaging in the diagnosis, management, and research of the condition. ABBREVIATIONS: AQP4 ϭ aquaporin 4; LESCL ϭ longitudinally extensive spinal cord lesion; MT ϭ magnetization transfer; NMO ϭ neuromyelitis optica

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“…Although only assessed by retrospective studies, the marked worsening of disability reported in some patients treated with interferon-β [19,20,[59][60][61][62], natalizumab [63][64][65], and fingolimod [66,67] should prompt us to avoid these therapies. Alemtuzumab, a T-and B-cell-depleting agent, was also shown to exacerbate NMOSD in single patients [51,68,69].…”

Section: Prevention Of Nmosd Attacks General Considerationsmentioning

confidence: 99%

Present and Future Therapies in Neuromyelitis Optica Spectrum Disorders

Kleiter

Gold

2016

Neurotherapeutics

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Neuromyelitis optica spectrum disorders (NMOSD) are important evolving entities, which have reached much attention in the recent years. NMOSD are characterized by inflammatory lesions in the optic nerves, spinal cord, and central parts of the brain, as well as an autoimmune process directed against aquaporin-4. As disability in NMOSD accumulates by inflammatory damage from attacks, both the treatment and prevention of attacks are decisive for the long-term outcome. NMOSD attacks are treated with highdose intravenous corticosteroids and apheresis therapies, in particular therapeutic plasma exchange. In cases of incomplete remission, escalation of attack treatment is recommended. Preventive therapy is immunosuppressive and should by commenced as early as possible. Apart from classical immunosuppressants such as azathioprine and mycophenolate mofetil, repurposed biologicals are increasingly used. B-cell depletion with rituximab and other agents, inhibition of the interleukin-6 receptor with tocilizumab, and blockade of complement-mediated damage by eculizumab all are promising therapeutic strategies evaluated in randomized controlled trials. In this review, we will discuss present and future immunotherapies for NMOSD and also consider combination of treatments, plasma, cellular and other therapies. Current advances in immunopathological knowledge are translated into innovative concepts and begin a new era of NMOSD therapy.

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IFNβ-1b may severely exacerbate Japanese optic-spinal MS in neuromyelitis optica spectrum

Abstract: Our study suggests that IFNβ-1b may trigger severe exacerbation in patients with the NMO spectrum. In INFβ-1b therapy, cases in NMO spectrum should be carefully excluded.

Cited by 178 publications

References 25 publications

Elevation of Sema4A Implicates Th Cell Skewing and the Efficacy of IFN-β Therapy in Multiple Sclerosis

Elevation of Sema4A Implicates Th Cell Skewing and the Efficacy of IFN-β Therapy in Multiple Sclerosis

Conventional and Advanced Imaging in Neuromyelitis Optica

Present and Future Therapies in Neuromyelitis Optica Spectrum Disorders

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