Cerebrospinal fluid antibodies to aquaporin-4 in neuromyelitis optica and related disorders: frequency, origin, and diagnostic relevance

Jarius, Sven; Franciotta, Diego; Paul, Friedemann; Ruprecht, Klemens; Bergamaschi, Roberto; Rommer, Paulus; Reuß, Reinhard; Probst, Christian; Kristoferitsch, Wolfgang; Wandinger, Klaus‐Peter; Wildemann, Brigitte

doi:10.1186/1742-2094-7-52

Cited by 186 publications

(180 citation statements)

References 38 publications

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“…In NMOsd, the CSF/serum albumin ratio (Q Alb ) - Alb CSF [mg/l]/Alb serum (g/l) - was performed to evaluate blood-brain barrier function. The upper limit was estimated as described elsewhere [11]. …”

Section: Methodsmentioning

confidence: 99%

Etiologic Spectrum and Prognosis of Longitudinally Extensive Transverse Myelopathies

Cobo‐Calvo¹,

Alentorn²,

Martínez³

et al. 2014

Eur Neurol

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Background: Patients with a first episode of longitudinal extensive transverse myelopathy (LETM) were reviewed with two objectives: to evaluate the clinical spectrum of LETM and to analyze the related clinical and laboratory variables that can be used as functional prognostic markers. Methods: A retrospective review was conducted of clinical, radiologic and biochemical data of patients admitted for LETM between 1993 and 2011. Results: Our cohort included 72 patients [median age 41 years, interquartile range (IQR) 29-61.5]. Median follow-up was 34 months (IQR 17.2-63). The modified Rankin Scale (mRS) score was ≥2 at the end of follow-up in 72.2%. The final diagnosis was idiopathic LETM in 22 patients, multiple sclerosis in 18, parainfectious disease in 11, systemic disease in 9, spinal cord infarction and neuromyelitis optica spectrum disorders in 3 patients each, and acute demyelinating encephalomyelitis, dural fistula, and tumor-related LETM in 2 patients each. Unfavorable outcome was associated with mRS ≥2 at admission [odds ratio (OR) 1.39, 95% confidence interval (CI) 1.16-1.66] and older age (OR 1.06, 95% CI 1.01-1.11). Conclusion: Idiopathic LETM was the most frequent diagnosis at the end of follow-up. Older age and clinically severe disease at onset were independent prognostic factors of poorer functional recovery.

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Section: Methodsmentioning

confidence: 99%

Etiologic Spectrum and Prognosis of Longitudinally Extensive Transverse Myelopathies

Cobo‐Calvo¹,

Alentorn²,

Martínez³

et al. 2014

Eur Neurol

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“…Klawiter and colleges reported the presence of CSF anti-AQP4 antibodies in three seronegative NMO patients (Klawiter et al, 2009), which could not be reproduced in other publications. Recently, Jarius et al, detected CSF anti-AQP4 antibodies in NMO-IgG seropositive patients exceeding anti-AQP4 antibody serum titers ≥ 1:250, but not in anti-AQP4 antibody negative patients (Jarius et al, 2010b). In cooperation with Dujmovic we analyzed the temporal dynamics of CSF anti-AQP4 antibodies in 12 patients with NMOSD (Dujmovic et al, 2011).…”

Section: Cerebrospinal Fluid Anti-aqp4 Antibodiesmentioning

confidence: 97%

“…In contrast, few studies focused on the presence and relevance of NMO antibodies in the CSF Klawiter et al, 2009;Jarius et al, 2010b;Dujmovic et al, 2011). Klawiter and colleges reported the presence of CSF anti-AQP4 antibodies in three seronegative NMO patients (Klawiter et al, 2009), which could not be reproduced in other publications.…”

Section: Cerebrospinal Fluid Anti-aqp4 Antibodiesmentioning

confidence: 99%

“…This leads to vascular hyalinization, necrosis, demyelination and axonal injury . The titer levels seem to have an impact on the disease pathogenesis as antibodies in the CSF are only detectable in high titer seropositive patients (Jarius et al, 2010b;Dujmovic et al, 2011). Latest findings indicated an influx of systemically produced anti-AQP4…”

Section: Pathogenic Role Of Anti-aqp4 Antibodies and T Cells In Nmomentioning

confidence: 99%

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Relevance of Autoantibodies for the Classification and Pathogenesis of Neurological Diseases

Mader¹,

Obholzer²,

Reindl³

2011

Autoimmune Disorders - Current Concepts and Advances From Bedside to Mechanistic Insights

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“…The samples were obtained before treatment with glucocorticoids or immunosuppressive agents. AQP4 antibodies were determined using a cell-based assay on an AQP4-transfected cell line from a commercial BIOCHIP kit 12,13 (EUROIMMUN AG, Lübeck, Germany).…”

Section: Aqp4 Antibody Testingmentioning

confidence: 99%

Serum-Positive and -Negative AQP4 Antibody NMO in Chinese Patients

Long

Liu

2012

Can. J. Neurol. Sci.

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232Neuromyelitis optica (NMO) is a severe idiopathic immunomediated inflammatory demyelinating and necrotizing disease that is characterized by transverse myelopathy and optic neuropathy. The exact etiology and mechanisms of NMO remain unknown. Serological and clinical evidence of B cell autoimmunity has been observed in a high proportion of patients, 1 suggesting a prominent role for humoral mechanisms in the pathogenesis of NMO. Neuromyelitis optica lesions show a marked deposition of immunoglobulins and complement in a characteristic perivascular rosette pattern along the outer rim of thickened vessel walls 2 . A specific IgG autoantibody, NMO-IgG, selectively targeting aquaporin 4 (AQP4), which accumulates in the central nervous system (CNS) microvessels, pia, subpia, and Virchow-Robin space, has been confirmed by indirect immunofluorescence with a composite substrate of mouse tissue 3,4 . According to this antibody, the new diagnostic criteria for NMO proposed by Wingerchuk et al facilitate its distinction from multiple sclerosis (MS) 5,6 . In subsequent studies, analysis of pathological brain lesions in NMO patients revealed a pattern of vasculocentric immune complex deposition and AQP4 loss ABSTRACT: Objective: To compare the clinical features of our sero-negative and sero-positive neuromyelitis optica (NMO) patients. Methods: Thirty-nine patients with NMO were recruited and analyzed retrospectively. Serum aquaporin 4 (AQP4) antibody status was determined by a cell-based assay. For the sero-negative patients, cerebrospinal fluid (CSF) and serum samples were re-tested using the cell-based assay and an indirect immunofluorescence assay. Results: By the cell-based assay, 30 patients (76.92%, 30/39), were positive for AQP4 antibodies in serum and 37 patients (94.9%, 37/39), had a CSF-positive antibody status. Seven NMO patients (17.9%, 7/39) were sero-negative by the cell-based assay but demonstrated positive CSF results. By indirect immunofluorescence, the remaining two patients, who had no AQP4 antibodies in serum or CSF by the cell-based assay, were positive for IgG antibodies in serum, which selectively targeted the central nervous system microvessels, pia, subpia, Virchow-Robin space, kidney, and stomach. There were no significant differences between the sero-positive and sero-negative NMO groups among their demographic and clinical data. Conclusions: Repeating the test using a different assay or CSF is helpful to clarify whether sero-negative NMO patients do in fact carry AQP4 antibodies. ORIGINAL ARTICLEidentical to that seen in NMO lesions, suggesting that AQP4 antibodies are related to NMO pathology 7,8 .Although more than 15 different immunoassays for the detection of AQP4 antibodies in patients with NMO have been developed, only a proportion of patients (33-91% among Western NMO cases and 41.7-91% among Japanese opticospinal MS (OSMS) are positive for AQP4 antibodies in serum 3,9,10 . In other words, the number of sero-negative NMO patients is not negligible.https://www.cambridge.org/core/terms. h...

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Cerebrospinal fluid antibodies to aquaporin-4 in neuromyelitis optica and related disorders: frequency, origin, and diagnostic relevance

Cited by 186 publications

References 38 publications

Etiologic Spectrum and Prognosis of Longitudinally Extensive Transverse Myelopathies

Etiologic Spectrum and Prognosis of Longitudinally Extensive Transverse Myelopathies

Relevance of Autoantibodies for the Classification and Pathogenesis of Neurological Diseases

Serum-Positive and -Negative AQP4 Antibody NMO in Chinese Patients

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