Evaluation of aquaporin‐4 antibody assays

Waters, Patrick; Pittock, Sean J.; Bennett, Jeffrey L.; Jarius, Sven; Weinshenker, Brian G.; Wingerchuk, Dean M.

doi:10.1111/cen3.12107

Cited by 120 publications

(115 citation statements)

References 57 publications

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“…Numerous studies have analyzed the correlation between AQP4-Ab titers and the stage of disease or the effectiveness of immunosuppressive therapy, 8–17 with conflicting results.…”

Section: Discussionmentioning

confidence: 99%

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Aquaporin-4 antibody titration in NMO patients treated with rituximab

Valentino

Marnetto

Granieri

et al. 2017

Neurol Neuroimmunol Neuroinflamm

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Objective:We undertook an observational retrospective study to investigate the usefulness of aquaporin-4 (AQP4) antibodies (Ab) titration in the management of patients with neuromyelitis optica (NMO) treated with rituximab (RTX) by studying (1) the correlation between AQP4-Ab titer and disease activity, (2) the influence of RTX on antibody levels, and (3) the association between AQP4-Ab levels and responsiveness to RTX.Methods:A cell-based assay was used for AQP4-Ab titration in 322 serum samples from 7 patients with NMO treated with RTX (median follow-up 65 months), according to a treatment-to-target approach. Serum samples were collected every month following standardized procedures.Results:(1) In group analysis, AQP4-Ab titers correlated with the disease activity, showing higher titers during and preceding relapses than during remission. However, in individual analysis, an increase in AQP4-Ab titers and CD19+ B cells did not always precede a relapse. (2) A reduction of AQP4-Ab titers in the short-term and long-term period was observed during RTX treatment. (3) Reduction of AQP4-Ab titers was observed in responder patients both 3 months after RTX infusion and in the long-term follow-up. In one nonresponder patient, AQP4-Ab levels never decreased during the treatment period.Conclusions:Titration of AQP4-Abs could be useful in the clinical management of patients with NMO treated with RTX: titration before each reinfusion and 3 months after each reinfusion may provide information about responsiveness to RTX. Although a relationship among AQP4-Ab levels, disease activity, and response to RTX was observed, the usefulness of AQP4-Ab titration to predict relapses is limited.

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“…Numerous studies have analyzed the correlation between AQP4-Ab titers and the stage of disease or the effectiveness of immunosuppressive therapy, 8–17 with conflicting results.…”

Section: Discussionmentioning

confidence: 99%

“…6,7 However, the usefulness of longitudinal AQP4-Abs titer measurements to predict further relapses or as an indicator of rituximab (RTX) efficacy remains to be evaluated in actual clinical practice. 8,9 …”

mentioning

confidence: 99%

Aquaporin-4 antibody titration in NMO patients treated with rituximab

Valentino

Marnetto

Granieri

et al. 2017

Neurol Neuroimmunol Neuroinflamm

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“…Subsequently, multiple investigators devised a variety of assays to detect AQP4-IgG in serum and CSF. Although the sensitivity and specificity of individual assays vary, AQP4-IgG seropositivity is generally considered to have 75% sensitivity and 99% specificity for disease (9,11–15). Importantly, AQP4 autoantibodies are typically undetected in clinically definite multiple sclerosis (MS) (9,12,16).…”

Section: Changing Face Of Neuromyelitis Optica: Aquaporin-4 Autoantibmentioning

confidence: 99%

“…Because of increased sensitivity (14,15,23), cell-based serum assays using microscopy-based or flow cytometry–based detection are recommended for AQP4-IgG serologic testing. Enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence (IIF) of tissue sections are typically less sensitive and often yield lower-titer and false-positive tests (24,25).…”

Section: Neuromyelitis Optica Spectrum Disorders: New International Cmentioning

confidence: 99%

Finding NMO: The Evolving Diagnostic Criteria of Neuromyelitis Optica

Bennett¹

2016

Journal of Neuro-Ophthalmology

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Neuromyelitis optica (NMO) is an autoimmune demyelinating disorder of the central nervous system (CNS) with predilection for the optic nerves and spinal cord. Since its emergence in the medical literature in the late 1800’s, the diagnostic criteria for NMO has slowly evolved from the simultaneous presentation of neurologic and ophthalmic signs to a relapsing or monophasic CNS disorder defined by clinical, neuroimaging, and laboratory criteria. Due to the identification of a specific autoantibody response against the astrocyte water channel aquaporin-4 (AQP4) in the vast majority of affected individuals, the clinical spectrum of NMO has greatly expanded necessitating the development of new international criteria for the diagnosis of NMO spectrum disorder (NMOSD). The routine application of new diagnostic criteria for NMOSD in clinical practice will be critical for future refinement and correlation with therapeutic outcomes.

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“…It is time to join efforts to facilitate access to the AQP4-IgG test throughout the national territory with the best available technique 9 . It is time to expand and establish the conditions to carry out the anti-MOG research in our country 10 .…”

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confidence: 99%

Neuromyelitis optica: it is time to move one step further

Adoni

2017

Arq. Neuro-Psiquiatr.

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N euromyelitis optica (NMO) is an autoimmune inflammatory channelopathy of the central nervous system mediated by serum antibodies against aquaporin-4 (AQP4-IgG), which affects mainly the optic nerves and the spinal cord . An International Panel of experts convened in 2015 and replaced the term NMO with NMO spectrum disorders (NMOSD) with the aim of including the typical limited forms of the syndrome, namely: myelitis, optic neuritis, area postrema syndrome, acute brainstem syndrome, acute diencephalic syndrome or narcolepsy, and symptomatic cerebral brain lesions with brain MRI findings of NMOSD. The exclusion of alternative diagnoses remains mandatory and, keeping this in mind, according to the Panel it is now possible to render the diagnosis of NMOSD even for those patients with AQP4-IgG status unknown 2 . The concept of a "spectrum" of NMO is very welcome in the hands of experts, taking into account the recurrent pattern of the disease and its severity, thus allowing early diagnosis and treatment. On the other hand, it can pose problems and diagnostic errors for the non-specialist. As a result, the best way to minimize errors and improve diagnostic accuracy in general is to know, as much as possible, the range of clinical manifestations of the disease as well as its behavior in the long term.In this issue of Arquivos de Neuropsiquiatria, Del Negro et al. 3 add clinical information about 34 Brazilian patients diagnosed with NMOSD and 40 patients with longitudinally extensive transverse myelitis (LETM). There are few differences from the previously published Brazilian series, which is not a weakness of the study but confirms our knowledge and reinforces the role of reliable science in replicating results. Worthy of note was the finding of autoimmunity markers more often in monophasic than in relapsing forms of NMO 4 . According to the authors, this finding may be a result of the small sample size. As for MRI, it would be interesting that the authors had verified the existence of bright spotty lesions (BSL, similar or higher in signal intensity than cerebrospinal fluid on the axial T2W images) given that these have been shown to be highly sensitive and specific in the diagnosis of LETM that occur in the context of NMOSD 5. Pekcevik et al. 6showed that BSL was found to be a specific finding (sensitivity: 64.6%; specificity: 89.1%) for differentiating NMO from MS and NMO from all the other causes of LETM.Del Negro et al.3 discuss the characteristics of other Brazilian series (in table 4) and a quick glance shows 155 cases of NMOSD patients studied since 2002. The problem of the small size of the series could be solved with multicenter studies and the creation of a national database 7 . A multicenter German study (NEMOS) was able to gather 175 patients with NMOSD 8 . Considering the continental dimensions of Brazil, we would be able to gather an even greater number of cases.We must realize that now is the time to take a step further, moving beyond papers that repeat and confirm to exhaustion the clinical and epide...

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Evaluation of aquaporin‐4 antibody assays

Cited by 120 publications

References 57 publications

Aquaporin-4 antibody titration in NMO patients treated with rituximab

Aquaporin-4 antibody titration in NMO patients treated with rituximab

Finding NMO: The Evolving Diagnostic Criteria of Neuromyelitis Optica

Neuromyelitis optica: it is time to move one step further

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