Frequency and prognostic impact of antibodies to aquaporin-4 in patients with optic neuritis

Jarius, Sven; Frederikson, Jette; Waters, Patrick; Paul, Friedemann; Akman‐Demir, Gülşen; Marignier, Romain; Franciotta, Diego; Ruprecht, Klemens; Kuenz, Bettina; Rommer, Paulus; Kristoferitsch, Wolfgang; Wildemann, Brigitte; Vincent, Angela

doi:10.1016/j.jns.2010.07.011

Cited by 154 publications

(127 citation statements)

References 36 publications

(59 reference statements)

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“…AQP4-Ab was positive in 78% (28/36) of the relapsing cases, and in 75% (3/4) of the monophasic cases. The median maximum longitudinal extension of spinal cord lesions did not differ between AQP4-Ab positive and AQP4-Ab negative NMOSD patients (5 [range, [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] and 5.5 [3 to 'entire spinal cord'], respectively), nor did the median total number of relapses (4.5 and 6, respectively).…”

Section: Resultsmentioning

confidence: 99%

Frequency and syndrome specificity of antibodies to aquaporin-4 in neurological patients with rheumatic disorders

Jarius

Jacobi

Seze³

et al. 2011

Mult Scler

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146

105

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Background: A new autoantibody (termed NMO-IgG, or AQP4-Ab) has recently been described in patients with neuromyelitis optica (NMO) and its formes frustes, longitudinally extensive transverse myelitis (LETM) and recurrent optic neuritis (rON). However, AQP4-Ab has been found also in patients with co-existing rheumatic diseases such as systemic lupus erythematosus (SLE) or Sjö gren's syndrome (SS), conditions which are characterized by broad, polyspecific B cell activation. Objectives: In this study, we aimed at evaluating the syndrome specificity and frequency of AQP4-Ab in patients with rheumatic diseases and neurological symptoms. Methods: For this purpose, serum samples from 109 neurological patients with established connective tissue disorders (CTD) (n ¼ 54), possible CTD (n ¼ 42), or vasculitis (n ¼ 13) were analysed for the presence of AQP4-Ab by a cellbased assay employing recombinant human AQP4. Results: AQP4-Ab was detectable in 31/40 (78%) patients with CTD and NMO spectrum disorders (median titre, 1:1000) but in none of the samples obtained from patients with CTD or vasculitis and neurological disorders other than NMO, LETM, or rON (n ¼ 69). Conclusion: The high syndrome specificity of the antibody for neuromyelitis optica spectrum disorders (NMOSDs) in patients with CTD supports the concept of AQP4-Ab being involved in the pathogenesis of these neurological conditions, and argues against AQP4-Ab simply being part of the polyclonal B cell activation generally associated with rheumatic diseases. Moreover, the finding that AQP4-Ab is present in patients with CTD and co-existing NMOSD with approximately the same frequency as in patients without CTD strengthens the case of CTD and AQP4-Ab positive NMOSD representing two co-existing yet distinct entities in the majority of patients.

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Section: Resultsmentioning

confidence: 99%

Frequency and syndrome specificity of antibodies to aquaporin-4 in neurological patients with rheumatic disorders

Jarius

Jacobi

Seze³

et al. 2011

Mult Scler

Self Cite

146

105

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“…62,63 Because of the heterogeneity of assays 61 and the possible harmful and ethical consequences of a false-negative or false-positive diagnosis of NMO-optic neuritis, we recommend that AQP4-IgG detection should be performed in laboratories that use validated assays with high sensitivity and specificity. Evidence exists, however, for a subgroup of patients with NMO who are AQP4-IgG seronegative but myelin oligodendrocyte glycoprotein IgG seropositive, so AQP4-IgG seronegativity does not necessarily preclude a diagnosis of NMO.…”

Section: Immunological Pathologymentioning

confidence: 99%

The investigation of acute optic neuritis: a review and proposed protocol

et al. 2014

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| Optic neuritis is an inflammatory optic neuropathy that affects many patients with multiple sclerosis (MS) at some point during their disease course. Differentiation of acute episodes of MS-associated optic neuritis from other autoimmune and inflammatory optic neuropathies is vital for treatment choice and further patient management, but is not always straightforward. Over the past decade, a number of new imaging, laboratory and electrophysiological techniques have entered the clinical arena. To date, however, no consensus guidelines have been devised to specify how and when these techniques can be most rationally applied for the diagnostic work-up of patients with acute optic neuritis. In this article, we review the literature and attempt to formulate a consensus for the investigation of patients with acute optic neuritis, both in standard care and in research with relevance to clinical treatment trials.

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“…However, we emphasize the high specificity of this test in our study to distinguish patients with a complete clinical diagnosis of NMO/NMOsd from those with a complete clinical diagnosis of MS. AQP4-ab has been recommended by Costa et al [11] to be tested only in patients whom the diagnosis is not clear (i.e., after considering clinical, brain/spinal cord MRI and OCBs) because they observed that 3.1% of the patients presenting with symptoms of the type seen in MS were positive for AQP4-ab. In a study of patients in Europe [12], AQP4-ab were detectable only in 5.8% (8/139) of patients with acute monosymptomatic ON. BON is typically associated with NMO and is rarely observed in MS.…”

Section: Discussionmentioning

confidence: 94%

Diagnostic Utility of Systematic Aquaporin-4 Antibodies Determination in the First Event of Immune-Mediated Optic Neuritis

Contentti

Virgiliis²,

Hryb³

et al. 2016

Eur Neurol

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Background: Antibodies against aquaporin-4 (AQP4-ab) have diagnostic and prognostic value. However, little is known to date about their utility in the first event of optic neuritis (ON). Objective: To evaluate the utility of systematic AQP4-ab determination in a retrospective cohort of patients with a first onset of ON. Patients and Methods: All patients (n = 42) were tested for AQP4-ab in the following context: typical ON (TON) and atypical ON (AON). Clinical, radiological and biochemical data were collected; patients with TON vs. AON and AQP4-ab positive vs. negative were compared. Results: The proportion of AQP4-ab seropositive patients was 40% in the TON group vs. 40.9% in the AON group. Visual acuity (VA) at baseline was poor in AON patients (p = 0.02) and these patients were associated with worse VA outcome (p < 0.001) at 6 months compared with TON patients, with a median follow-up of 3.27 ± 1.79 years. Brain MRI with dissemination in space criteria (p < 0.001), spinal cord partial lesions (p < 0.001) and oligoclonal bands (p = 0.02) were associated with the initial stages of TON. VA severity, number of myelitis attacks and ON relapses did not differ significantly between seropositive and seronegative patients. AQP4-ab were detected only in neuromyelitis optica spectrum disorders patients. Conclusion: This study showed a high seropositivity for AQP4-ab in TON patients, suggesting that it could diagnostic utility at the onset of ON.

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Frequency and prognostic impact of antibodies to aquaporin-4 in patients with optic neuritis

Cited by 154 publications

References 36 publications

Frequency and syndrome specificity of antibodies to aquaporin-4 in neurological patients with rheumatic disorders

Frequency and syndrome specificity of antibodies to aquaporin-4 in neurological patients with rheumatic disorders

The investigation of acute optic neuritis: a review and proposed protocol

Diagnostic Utility of Systematic Aquaporin-4 Antibodies Determination in the First Event of Immune-Mediated Optic Neuritis

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