Lennon, V. A. et al. A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet 364, 2106-2112

Department of Neurology, Mayo Clinic Rochester, Rochester, MN 55905, USA.
The Lancet (Impact Factor: 45.22). 12/2004; 364(9451):2106-12. DOI: 10.1016/S0140-6736(04)17551-X
Source: PubMed


Neuromyelitis optica is an inflammatory demyelinating disease with generally poor prognosis that selectively targets optic nerves and spinal cord. It is commonly misdiagnosed as multiple sclerosis. Neither disease has a distinguishing biomarker, but optimum treatments differ. The relation of neuromyelitis optica to optic-spinal multiple sclerosis in Asia is uncertain. We assessed the capacity of a putative marker for neuromyelitis optica (NMO-IgG) to distinguish neuromyelitis optica and related disorders from multiple sclerosis.
Indirect immunofluorescence with a composite substrate of mouse tissues identified a distinctive NMO-IgG staining pattern, which we characterised further by dual immunostaining. We tested masked serum samples from 102 North American patients with neuromyelitis optica or with syndromes that suggest high risk of the disorder, and 12 Japanese patients with optic-spinal multiple sclerosis. Control patients had multiple sclerosis, other myelopathies, optic neuropathies, and miscellaneous disorders. We also established clinical diagnoses for 14 patients incidentally shown to have NMO-IgG among 85000 tested for suspected paraneoplastic autoimmunity.
NMO-IgG outlines CNS microvessels, pia, subpia, and Virchow-Robin space. It partly colocalises with laminin. Sensitivity and specificity were 73% (95% CI 60-86) and 91% (79-100) for neuromyelitis optica and 58% (30-86) and 100% (66-100) for optic-spinal multiple sclerosis. NMO-IgG was detected in half of patients with high-risk syndromes. Of 14 seropositive cases identified incidentally, 12 had neuromyelitis optica or a high-risk syndrome for the disease.
NMO-IgG is a specific marker autoantibody of neuromyelitis optica and binds at or near the blood-brain barrier. It distinguishes neuromyelitis optica from multiple sclerosis. Asian optic-spinal multiple sclerosis seems to be the same as neuromyelitis optica.

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Available from: Ichiro Nakashima, Jan 03, 2014
    • "Ota). identified in 2004 (Lennon et al., 2004, 2005). This antibody binds aquaporin 4 (AQP4), which is expressed at the cell membrane of astrocytes present in the main water channel of the blood–brain barrier. "
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    ABSTRACT: Background: Neuromyelitis optica spectrum disorder (NMOSD) differs from multiple sclerosis (MS) by prognosis and approach to treatment, and it is thus important to distinguish NMOSD from MS. Objective: We evaluated the structural brain abnormalities in patients with NMOSD and with relapsing-remitting MS (RRMS) using with MRI. Methods: Twenty-one NMOSD patients with antibodies against aquaporin 4, 32 patients with RRMS, and current age- and sex- matched 39 healthy subjects underwent 3-T MRI. The differences in gray matter volume and fractional anisotropy (FA) value among the three groups were evaluated. Results: There were significant global gray matter volume reductions of NMOSD and RRMS groups, compared to the healthy subjects. Significant and diffuse decreases in FA values were observed in both the NMOSD and RRMS patients. Significant gray matter volume and FA value reductions of the RRMS patients in the bilateral thalami and some regions were observed compared to the NMOSD patients. Conclusion: Larger brain structural changes were seen in the RRMS group compared to the NMOSD group, and among them, the thalamus was revealed as the important region for the discrimination of these two diseases. MRI analyses of the brain may be helpful in differentiating NMOSD from RRMS patients.
    No preview · Article · Nov 2015 · Multiple Sclerosis and Related Disorders
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    • "n¼ 7 n¼ 933 TBA Cabrera-Gómez et al. (2009) n¼ 48 n¼ 89 TBA Chan et al. (2010) n¼ 18 n¼ 92 CBA, TBA Dellavance et al. (2012) n¼ 47 n¼ 638 TBA Etemadifar et al. (2012) n¼ 33 n¼ 32 TBA Fazio et al. (2009) n¼ 33 n¼ 87 CBA, TBA, ELISA Hayakawa et al. (2008) n¼ 21 n¼ 212 ELISA Höftberger et al. (2013) n¼ 103 n¼ 122 CBA, TBA Ketelslegers et al. (2011) n¼ 36 n¼ 246 CBA W. Kim et al. (2012) n¼ 64 n¼ 209 ELISA Y.-J. Kim et al. (2012) n¼ 9 n¼ 140 CBA, TBA, ELISA Lennon et al. (2004) n¼ 45 n¼ 22 TBA Long et al. (2012b) n¼ 44 n¼ 99 CBA Long et al. (2012c) n¼ 39 n¼ 62 CBA Mader et al. (2010) n¼ 30 n¼ 234 CBA Marignier et al. (2008) n¼ 26 n¼ 95 TBA Marnetto et al. (2009) n¼ 16 n¼ 66 CBA McKeon et al. (2009) n¼ 40 n¼ 735 TBA Nagaishi et al. (2011) n¼ 0 n¼ 80 CBA Pisani et al. (2013) n¼ 40 n¼ 72 CBA Pittock et al. (2008) n¼ 78 n¼ 33 TBA Siritho et al. (2011) n¼ 23 n¼ 69 CBA Takahashi et al. (2007) n¼ 22 n¼ 113 CBA Unni et al. (2013) n¼ 21 n¼ 12 CBA Waters et al. (2008) n¼ 25 n¼ 78 CBA, TBA Woodhall et al. (2013) n¼ 20 n¼ 0 CBA Wu et al. (2011) n¼ 27 n¼ 156 CBA, ELISA Yang et al. (2014) n ¼ 44 n¼ 117 CBA Yang et al. (2013) n¼ 53 n¼ 115 CBA R. Ruiz-Gaviria et al. / Multiple Sclerosis and Related Disorders 4 (2015) 345–349 347 glycoprotein (Woodhall et al., 2013; Sato et al., 2014; Sato et al., 2014). This study, however did not address that important group of patients with unclear diagnosis, which are perhaps those that would gain more from a good diagnostic tool. "
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    ABSTRACT: Antibodies against water channel protein aquaporin 4 (AQP4) in astrocytes play a role in the etiology and physiopathology of neuromyelitis optica (NMO); detection of this immunoglobulin in serum is highly suggestive of this diagnosis. There are several immunoassays to detect the antibody with different sensitivities and specificities. We conducted a meta-analysis to determine the overall diagnostic accuracy from these tests. We conducted a systematic review in five different electronic databases: Pubmed, Embase, The Cochrane Library, Scopus, Database of Abstracts of Reviews of Effect (DARE) and Lilacs. We included both case control and consecutive enrollment studies that evaluated the performance of the immunoassays in patients with suspected NMO in comparison with the 2006 Wingerchuk diagnostic criteria. Articles were assessed by two different reviewers, who also extracted data. 30 studies for three different immunoassays were included in the meta-analysis. To obtain a summary estimate for the sensitivity and specificity with 95% confidence interval a bivariate random effect model was used. The approximated sensitivity for the cell based assay (CBA), the tissue-based assay (TBA) and the ELISA test were 0.76(95% CI 0.67-0.82), 0.59(95% CI 0.50-0.67), and 0.65(95% CI 0.53-0.75) respectively. The mean specificity of the CBA was 0.99 (95% CI 0.97-0.99), TBA 0.98 (95% CI 0.97-0.99) and ELISA 0.97(95% CI 0.96-0.99). AQP4 detection in serum with immunoassay is a great tool for the diagnosis of patients with NMO, due to the high specificity, allowing the clinician to differentiate this disease from other neurological conditions that resemble NMO. Copyright © 2015 Elsevier B.V. All rights reserved.
    Full-text · Article · Jun 2015
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    • "The presence of oligoclonal bands (OCB) of immunoglobulin G (IgG) restricted to the CSF is detected in only 15–30% of the patients [1]. The detection of AQP4-IgG is considered a serum biomarker [7] [8] contributing to the diagnosis of NMO and to broaden its clinical spectrum. However, the AQP4-IgG seropositive rate depends on the assay type used [8] [9] [10] [11]. "
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    ABSTRACT: Neuromyelitis Optica (NMO) is an inflammatory demyelinating disease of the CNS. There have been few epidemiologic studies on NMO, none in Portugal. To analyze the clinical, biological and MRI characteristics from a cohort of Portuguese patients who fulfilled the Wingerchuk 2006 NMO/NMOSD criteria. To identify and characterize those who had concomitant autoimmune disease or circulating autoantibodies. We performed an observational, retrospective, multicenter study in 5 Hospital Centers in Portugal. Sixty-seven patients fulfilled the inclusion criteria. They were mainly Caucasian, 55 female. Median age at onset was 32.0 years and mean follow-up 7.4±6.0 years. Twenty-one patients were definite NMO and optic neuritis (ON) the most frequent initial presentation. Forty-six were classified as NMO spectrum disorders. The main subtypes were recurrent ON and single longitudinally extensive transverse myelitis. Twenty-four patients had positive AQP4-IgG. Twenty-three had other circulating autoantibodies. Fifteen out of 67 patients had concomitant autoimmune disease. There was a significant correlation between the presence of autoimmune disease and the positivity for AQP4-IgG. Five patients died, all definite NMO. This is the first study about this rare disease in Portugal. Demographic features were similar to other studies. The existence of concomitant autoimmune disease was significantly associated with seropositivity for AQP4-IgG. Copyright © 2015 Elsevier B.V. All rights reserved.
    Full-text · Article · Apr 2015 · Clinical Neurology and Neurosurgery
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