Neuromyelitis optica: Passive transfer to rats by human immunoglobulin

Kinoshita, Makoto; Nakatsuji, Yuji; Kimura, Takashi; Moriya, M.; Takata, Ken; Okuno, Tatsusada; Kumanogoh, Atsushi; Kajiyama, Koji; Yoshikawa, Hiroaki; Sakoda, Saburo

doi:10.1016/j.bbrc.2009.06.085

Cited by 226 publications

(172 citation statements)

References 22 publications

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“…A growing body of evidence suggests that AQP4-Abs play a pathogenic role in NMO (6,7,(10)(11)(12) (10). However, this study has not excluded a possible role of AQP4-Abs produced in the peripheral blood.…”

Section: Discussionmentioning

confidence: 67%

“…It was also demonstrated that direct injection of IgGs derived from NMO patients into the brains of naïve mice did not cause NMO-like lesions, although brain tissue destruction associated with leukocyte infiltration was elicited by coinjecting human complement (9). Other groups have shown that the passive transfer of IgGs from NMO patients to rats challenged with induction of experimental autoimmune encephalomyelitis (EAE) may cause a decrease in the expression of AQP4 in astrocytes along with worsening of clinical EAE (10)(11)(12). In contrast, the transfer of IgGs to unimmunized rats did not cause any pathology.…”

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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: 67%

mentioning

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

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“…Among others, the demonstration in animal models 9,10 (induction of transfer experimental autoimmune encephalomyelitis accompanied by the administration of immunoglobulins from AQP-4 antibody positive patients) that AQP-4 antibody activates complement, induces astrocytic damage and other features of NMO lesions, with a relative preservation of myelin basic protein staining as previously reported in pathological studies with NMO patients has provided evidence in vivo that AQP-4 antibody is pathogenic in the presence of T cellmediated brain inflammation.…”

Section: Introductionmentioning

confidence: 74%

Atypical presentations of neuromyelitis optica

Sato

Fujihara

2011

Arq. Neuro-Psiquiatr.

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Neuromyelitis optica (NMO) is an inflammatory disease of central nervous system classically characterized by acute, severe episodes of optic neuritis and longitudinally extensive transverse myelitis, usually with a relapsing course. The identification of an autoantibody exclusively detected in NMO patients against aquaporin-4 (AQP-4) has allowed identification of cases beyond the classical phenotype. Brain lesions, once thought as infrequent, can be observed in NMO patients, but lesions have different characteristics from the ones seen in multiple sclerosis. Additionally, some AQP-4 antibody positive patients may present with a variety of symptoms not being restricted to optic neuritis and acute myelitis during the first attack or in a relapse. Examples are not limited to, but may include patients only with brain and/or brainstem lesions, narcolepsy with hypothalamic lesions or patients with intractable hiccups, nausea and vomiting. The prompt identification of NMO patients with atypical presentations may benefit these patients with institution of early treatment to reduce disability and prevent further attacks. Key words: neuromyelitis optica, aquaporin 4, myelitis, optic neuritis, diagnosis, differential, nausea, vomiting, hiccup, brain diseases.Apresentações atípicas da neuromielite óptica RESUMO Neuromielite óptica (NMO) é uma doença inflamatória do sistema nervoso central caracterizada classicamente por neurite óptica grave e mielite transversa longitudinalmente extensa, com um curso usualmente recorrente. A identificação do anticorpo detectado exclusivamente nos pacientes com NMO contra a aquaporina-4 (AQP-4) permitiu a identificação de casos além do fenótipo clássico. Lesões cerebrais, que antes eram descritas como infrequentes, podem ser observadas em pacientes com NMO, mas as lesões possuem características diferentes das lesões observadas na esclerose múltipla. Além disso, alguns pacientes positivos para o anticorpo contra a AQP-4 podem apresentar uma variedade de sintomas não restritos à neurite óptica e mielite aguda, seja durante o primeiro ataque seja em uma recorrência. Exemplos não estão limitados aos descritos a seguir, mas incluem pacientes com lesões cerebrais e/ou tronco cerebral, narcolepsia com lesões hipotalâmicas ou pacientes com quadros intratáveis de soluços, náusea e vômitos. A identificação rápida dos pacientes com NMO com apresentações atípicas pode beneficiar estes pacientes com a instituição precoce do tratamento a fim de reduzir a incapacidade e prevenir ataques subsequentes. Palavras-Chave: neuromielite óptica, aquaporina 4, mielite, neurite óptica, diagnóstico diferencial, náusea, vômito, soluço, encefalopatias.

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“…Rats that were intrathecally injected with IgG from patients with anti-amphiphysin antibody-positive stiffperson syndrome, showed anxiety-like behaviors, as evaluated by the elevated plus-maze test and open-field test (Geis et al 2012). Histological evidence related to antibodymediated central nervous system disorders has been provided in rodent models of anti-aquaporin 4 antibody (AQP4)-mediated neuromyelitis optica (NMO) (Bradl et al 2009;Kinoshita et al 2009;Saadoun et al 2010). However, these animals did not exhibit specific symptoms that are observed in NMO patients.…”

Section: Discussionmentioning

confidence: 99%

Induction of Memory Deficit in Mice with Chronic Exposure to Cerebrospinal Fluid from Patients with Anti-<i>N</i>-Methyl-D-Aspartate Receptor Encephalitis

Tanaka

Wang

et al. 2015

Tohoku J. Exp. Med.

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Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is now widely recognized and the patients with this disease show prominent psychiatric symptoms followed by seizures, respiratory failure, involuntary movement, autonomic instability, and amnesia. The anti-NMDAR antibody titer coincides with disease activity, and antibody-deprivation treatment ameliorates neurological symptoms. Previous studies have shown that clusters of NMDARs on the neuronal surface decrease in density upon incubation with the cerebrospinal fluid from patients (NMDAR-CSF), and that the induction of long-term potentiation, a cellular mechanism underlie learning and memory processes, was suppressed with NMDAR-CSF. In this study, we exposed mice to NMDAR-CSF in an attempt to reproduce the human symptoms in mice. CSF was continuously administered via a cannula placed in the lateral ventricle of the mouse that connected to an osmotic pump transplanted in the back of the mouse. From day 8-18, we evaluated the behavior of the mice using standardized tests that were performed serially. Mice exposed to NMDAR-CSF showed impaired spatial memory, as detected with the Morris water maze test. Brain tissue from mice with memory disturbances had decreased content of NMDAR protein in the hippocampal area shown by immunohistochemistry, which is consistent with the anti-NMDAR antibodies affect the expression and function of NMDARs, resulting in anti-NMDAR encephalitis-like symptoms. Also, the mice treated with the NMDAR-CSF did not show inflammatory cell infiltration or neuron loss in their brain tissue and this lack of nervous tissue destruction is encouraging as it is consistent with the idea that this disease can be treated through immunotherapy.

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Neuromyelitis optica: Passive transfer to rats by human immunoglobulin

Cited by 226 publications

References 22 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

Atypical presentations of neuromyelitis optica

Induction of Memory Deficit in Mice with Chronic Exposure to Cerebrospinal Fluid from Patients with Anti-<i>N</i>-Methyl-D-Aspartate Receptor Encephalitis

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