Establishment of a New Sensitive Assay for Anti-Human Aquaporin-4 Antibody in Neuromyelitis Optica

Takahashi, Toshiyuki; Fujihara, Kazuo; Nakashima, Ichiro; Misu, Tatsuro; Miyazawa, Isabelle; Nakamura, Masashi; Watanabe, Shohei; Ishii, Naoto; Itoyama, Yasuto

doi:10.1620/tjem.210.307

Cited by 156 publications

(105 citation statements)

References 18 publications

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“…Serum AQP4 antibody (in an assay using AQP4-transfected human embryonic kidney cells [Takahashi et al 2006) and oligoclonal IgG bands were positive.…”

Section: Impairmentmentioning

confidence: 99%

A Prominent Elevation of Glial Fibrillary Acidic Protein in the Cerebrospinal Fluid during Relapse in Neuromyelitis Optica

Takano

Misu

Takahashi

et al. 2008

Tohoku J. Exp. Med.

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Neuromyelitis optica (NMO) is a neurologic disease characterized by severe optic neuritis, longitudinally extended, transverse myelitis and serum aquaporin-4 (AQP4) antibody. Our recent neuropathological study revealed the extensive loss of AQP4 and glial fibrillary acidic protein (GFAP), an astrocyte-specific protein, in NMO lesions, but not in MS lesions, suggesting that severe astrocytic damage or dysfunction may be related to the pathogenesis of NMO. Here we report a patient of NMO, in which the cerebrospinal fluid (CSF) levels of GFAP were measured both during relapse of myelitis and after high-dose intravenous methylprednisolone (HIMP). The patient was a 34-year old woman with two previous episodes of optic neuritis. She developed myelitis longitudinally extending from C3 to T12 with contrast enhancement, and was AQP4 antibody-positive. In the acute phase, the GFAP level in the cerebrospinal fluid (CSF) was prominently elevated (18,966.7 ng/ml) as compared with controls (0.6 ± 0.33 ng/ml). However, following HIMP, the clinical and MRI findings improved, and the CSF-GFAP level was near-normal (2.1 ng/ml). The CSF of myelin basic protein was also elevated in relapse (1,016.0 pg/ml), and became lower but still remained high (158.7 pg/ml) after HIMP compared with controls (3.36 ± 3.83 pg/ml). The prominent elevation of the CSF-GFAP level in relapse of NMO, followed by its sharp decline after therapy, suggests severe astrocytic damage with a temporal profile distinct from that of the demyelinating process in NMO. CSF-GFAP may be useful as a biomarker of NMO.glial fibrillary acidic protein (GFAP); neuromyelitis optica; cerebrospinal fluid; myelin basic protein; relapse. Neuromyelitis optica (NMO) is a neurologic disease characterized by severe, often bilateral optic neuritis and transverse myelitis. As well as the unique lesion distribution and severe functional disability in NMO, the clinical and laboratory features of NMO have been reported to be distinct from those of MS, and they include female preponderance, higher onset age, mostly

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“…Serum AQP4 antibody (in an assay using AQP4-transfected human embryonic kidney cells [Takahashi et al 2006) and oligoclonal IgG bands were positive.…”

Section: Impairmentmentioning

confidence: 99%

A Prominent Elevation of Glial Fibrillary Acidic Protein in the Cerebrospinal Fluid during Relapse in Neuromyelitis Optica

Takano

Misu

Takahashi

et al. 2008

Tohoku J. Exp. Med.

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“…The serum antibody has been variably detected in different populations 22 . Currently available assays include a tissue-based indirect immunofluorescence (IIF) assay; ELISA; fluorescence immunoprecipitation assay (FIPA) 23,24 ; fluorescence-activated cell sorting (FACS) assay; and visual fluorescence-observation cell-based assay (CBA) [24][25][26] . A recent international comparative study of the different techniques to detect AQP4-IgG in sera of patients with NMO and NMOSD showed that, although their specificities were excellent, their sensitivities were variable 27 .…”

Section: Aquaporin 4-igg Assaysmentioning

confidence: 99%

The expanded spectrum of neuromyelitis optica: evidences for a new definition

Lana-Peixoto

Callegaro

2012

Arq. Neuro-Psiquiatr.

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Neuromyelitis optica (NMO) has been traditionally described as the association of recurrent or bilateral optic neuritis and longitudinally extensive transverse myelitis (LETM). Identification of aquaporin-4 antibody (AQP4-IgG) has deeply changed the concept of NMO. A spectrum of NMO disorders (NMOSD) has been formulated comprising conditions which include both AQP4-IgG seropositivity and one of the index events of the disease (recurrent or bilateral optic neuritis and LETM). Most NMO patients harbor asymptomatic brain MRI lesions, some of them considered as typical of NMO. Some patients with aquaporin-4 autoimmunity present brainstem, hypothalamic or encephalopathy symptoms either preceding an index event or occurring isolatedly with no evidence of optic nerve or spinal involvement. On the opposite way, other patients have optic neuritis or LETM in association with typical lesions of NMO on brain MRI and yet are AQP4-IgG seronegative. An expanded spectrum of NMO disorders is proposed to include these cases.

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“…These elegant experiments conclusively proved that the antigen recognized by the NMO-IgG antibody was AQP4. Both the immunohistochemical and the AQP4-transfected HEK cell assays for detecting anti-AQP4 antibody from patient sera were subsequently validated by several groups (Takahashi et al, 2006;Paul et al, 2007;Marignier et al, 2008;Kalluri et al, 2010). These studies definitively prove that the NMO-IgG is an anti-AQP4 antibody.…”

Section: Acute Inflammatory Myelopathies 637mentioning

confidence: 91%

Acute inflammatory myelopathies

Cree

2014

Handbook of Clinical Neurology

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Establishment of a New Sensitive Assay for Anti-Human Aquaporin-4 Antibody in Neuromyelitis Optica

Cited by 156 publications

References 18 publications

A Prominent Elevation of Glial Fibrillary Acidic Protein in the Cerebrospinal Fluid during Relapse in Neuromyelitis Optica

A Prominent Elevation of Glial Fibrillary Acidic Protein in the Cerebrospinal Fluid during Relapse in Neuromyelitis Optica

The expanded spectrum of neuromyelitis optica: evidences for a new definition

Acute inflammatory myelopathies

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