Pathologic and immunologic profiles of a limited form of neuromyelitis optica with myelitis

Yanagawa, Kaori; Kawachi, Izumi; Toyoshima, Yasuko; Yokoseki, Akio; Arakawa, Masato; Hasegawa, Akiko; Ito, Takui; Kojima, Naoya; Koike, Ryuji; Tanaka, Keiko; Kosaka, Takayuki; Tan, CT; Kakita, Akiyoshi; Okamoto, Kouichirou; Teräs, Mika; Sakimura, Kenji; Takahashi, Hitoshi; Nishizawa, Masatoyo

doi:10.1212/wnl.0b013e3181c1deb9

Cited by 87 publications

(81 citation statements)

References 34 publications

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“…It would be interesting to investigate which organs blood PB move to during the course of NMO. The levels of IL-6 in the serum and CSF are elevated in NMO compared with HS or CMS patients (27,28). In this regard, it is of note that blocking IL-6R signaling was found to dramatically reduce the survival of PB ex vivo, which was dependent on the presence of autologous serum containing IL-6.…”

Section: Discussionmentioning

confidence: 99%

“…IL-6 induces B-cell differentiation into plasma cells, maintains early plasma cell survival, and enhances plasma cell IgG secretion (24). Besides, IL-6 is elevated in the cerebrospinal fluid (CSF) or peripheral blood of NMO patients compared with that of CMS patients and HS (27,28). In a rodent autoimmunity model, IL-6 deficiency caused impaired autoantibody secretion by B cells (29).…”

Section: Expanded Cells Resemble Early Plasma Cells In Gene Expressiomentioning

confidence: 99%

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Interleukin 6 signaling promotes anti-aquaporin 4 autoantibody production from plasmablasts in neuromyelitis optica

Chihara

Aranami

Sato

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

402

297

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Neuromyelitis optica (NMO) is an inflammatory disease affecting the optic nerve and spinal cord, in which autoantibodies against aquaporin 4 (AQP4) water channel protein probably play a pathogenic role. Here we show that a B-cell subpopulation, exhibiting the CD19 int CD27 high CD38 high CD180 − phenotype, is selectively increased in the peripheral blood of NMO patients and that anti-AQP4 antibodies (AQP4-Abs) are mainly produced by these cells in the blood of these patients. These B cells showed the morphological as well as the phenotypical characteristics of plasmablasts (PB) and were further expanded during NMO relapse. We also demonstrate that interleukin 6 (IL-6), shown to be increased in NMO, enhanced the survival of PB as well as their AQP4-Ab secretion, whereas the blockade of IL-6 receptor (IL-6R) signaling by anti-IL-6R antibody reduced the survival of PB in vitro. These results indicate that the IL-6-dependent B-cell subpopulation is involved in the pathogenesis of NMO, thereby providing a therapeutic strategy for targeting IL-6R signaling.neuroinflamatory disease | autoimmunity | multiple sclerosis | central nervous system | IL-6 receptor blockade N euromyelitis optica (NMO) is an inflammatory demyelinating disorder characterized by recurrent attacks of severe optic neuritis and myelitis. Unlike the conventional form of multiple sclerosis (CMS), the lesions of NMO tend to spare the cerebral white matter, especially during the early stage (1), and even a single episode of attack can cause serious neurological deficits such as total blindness and paraplegia. Accordingly, accumulation of irreversible damage to the central nervous system (CNS) along with rapid progression of disability is more frequently found in NMO compared with CMS (2).NMO can be distinguished from CMS by clinical, neuroimaging, and serological criteria (3). It is now known that serum anti-aquaporin 4 (AQP4) autoantibodies can be used as a disease marker of NMO (1, 2). AQP4 is the most abundantly expressed water channel protein in the CNS and is highly expressed in the perimicrovessel astrocyte foot processes, glia limitans, and ependyma (4). Emerging clinical and pathological observations suggest that anti-AQP4 antibodies (AQP4-Abs) play a key role in the pathogenesis of NMO. Prior studies have documented a significant correlation of serum AQP4-Ab levels with the therapeutic efficacy of plasma exchange during clinical exacerbations of NMO (2, 5). In the CNS lesions of NMO, reduced expression of AQP4 on astrocytes is evident even during the early stage (6), which is followed by the occurrence of vasculocentric destruction of astrocytes associated with perivascular deposition of complement and IgG (7).On the other hand, recent studies have suggested that AQP4-Abs alone are incapable of causing the clinical and pathological features of NMO. In fact, Hinson et al. emphasized the role of cellular immunity in combination with AQP4-Abs by showing that the attack severity of NMO was not correlated with serum AQP4-Ab levels (8). It was also d...

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Section: Discussionmentioning

confidence: 99%

Section: Expanded Cells Resemble Early Plasma Cells In Gene Expressiomentioning

confidence: 99%

Interleukin 6 signaling promotes anti-aquaporin 4 autoantibody production from plasmablasts in neuromyelitis optica

Chihara

Aranami

Sato

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

402

297

View full text Add to dashboard Cite

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“…Even in cases without optic neuritis, the detection of anti-AQP4 antibody in patients with myelitis allows the diagnosis of a limited form of NMO, i.e. an NMO spectrum disorder (5,6).…”

Section: Introductionmentioning

confidence: 99%

Recurrent Spinal Cord Attacks in a Patient with a Limited Form of Neuromyelitis Optica

et al. 2011

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This report describes the case of a 71-year-old woman with a limited form of neuromyelitis optica (NMO) who had a longitudinally extensive spinal cord lesion from the fourth to the tenth thoracic vertebrae. Up to age 75, she had four subsequent recurrences of the myelitis within the same spinal cord area but with no optic neuritis. Anti-AQP4 antibody was seropositive. Recurrence within the same spinal cord area might be a characteristic clinical finding in NMO spectrum disorders. For such patients, examination for anti-AQP4 antibody might be necessary for the diagnosis and therapy of this disorder.

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“…Conditions other than intramedullary spinal cord tumors including anterior spinal artery syndrome, neuromyelitis optica 16 and sarcoidosis, 17 and so on, sometimes show acute or subacute progressive myelopathy and MRI findings mimicking intramedullary tumor. Careful differential diagnosis is necessary and biopsy should be considered before treatment.…”

Section: Discussionmentioning

confidence: 99%

Progression of paralysis is the most useful factor for differentiating malignant from benign intramedullary tumors

et al. 2012

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Study design: Retrospective study. Objectives: The purpose of this study was to identify the clinical factors for differentiating malignant from benign intramedullary spinal cord tumors. Setting: Niigata, Japan. Methods: We conducted a retrospective review of charts and images. Preoperative paralysis including walking ability, urinary function, magnetic resonance imaging (MRI) findings and pathological diagnosis were evaluated in 33 consecutive cases of intramedullary spinal cord tumor, and the clinical factors that were useful for differentiating malignant from benign tumors were identified. Results: Early progression of paralysis was the most valuable feature for differentiating malignant from benign tumors. Malignant tumors were suspected in only three of ten cases on the basis of MRI findings. Conclusion: Simple assessment of walking ability is easy to perform and is useful for predicting the pathological malignancy of intramedullary tumors of the spinal cord.

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Pathologic and immunologic profiles of a limited form of neuromyelitis optica with myelitis

Cited by 87 publications

References 34 publications

Interleukin 6 signaling promotes anti-aquaporin 4 autoantibody production from plasmablasts in neuromyelitis optica

Interleukin 6 signaling promotes anti-aquaporin 4 autoantibody production from plasmablasts in neuromyelitis optica

Recurrent Spinal Cord Attacks in a Patient with a Limited Form of Neuromyelitis Optica

Progression of paralysis is the most useful factor for differentiating malignant from benign intramedullary tumors

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