scholarly journals A Small-molecule Screen Yields Idiotype-specific Blockers of Neuromyelitis Optica Immunoglobulin G Binding to Aquaporin-4

2012 ◽  
Vol 287 (44) ◽  
pp. 36837-36844 ◽  
Author(s):  
Puay-Wah Phuan ◽  
Marc O. Anderson ◽  
Lukmanee Tradtrantip ◽  
Hua Zhang ◽  
Joseph Tan ◽  
...  
2020 ◽  
Vol 13 ◽  
pp. 175628641989859
Author(s):  
Wei Fang* ◽  
Yang Zheng* ◽  
Fan Yang ◽  
Meng-Ting Cai ◽  
Chun-Hong Shen ◽  
...  

Background: Short segment myelitis (SSM, < 3 vertebral segments) is an under-recognized initial manifestation of neuromyelitis optica spectrum disorders (NMOSD). Though infrequent, failure to recognize SSM in patients with NMOSD would lead to incorrect diagnosis and treatment. Therefore, delineation of features of NMOSD-associated SSM is of paramount importance. Objective: Our study aimed to determine the demographic, clinical and radiological features of NMOSD-associated SSM, and compare those with NMOSD-associated longitudinally extensive transverse myelitis (LETM) and multiple sclerosis (MS)-associated SSM, respectively. Methods: Chinese patients presenting initially only with acute myelitis and diagnosed with NMOSD ( n = 46) and MS ( n = 11) were included. Clinical, serological, imaging and disability data were collected. Mann–Whitney U test or two-tailed Fisher’s exact tests were used to analyse the data. Results: Of the 46 enrolled NMOSD patients, 34 (74%) collectively had 38 LETM lesions, while 12 (26%) had 14 SSM lesions. When compared with LETM, NMOSD presenting with SSM were more likely to have a delayed diagnosis and a lower level of disability at nadir during the first attack. T1-weighted imaging hypointensity was more prominent in NMOSD-associated LETM lesions than NMOSD-associated SSM lesions. When compared with MS-associated SSM, NMOSD-associated SSM lesions were more likely to be centrally located, grey matter involving and transversally extensive on axial imaging and spanned no less than 2 vertebral segments on sagittal imaging. Conclusion: These findings suggest that SSM does not preclude the possibility of a NMOSD diagnosis. Testing for serum aquaporin-4 immunoglobulin G (AQP4-IgG) and careful study of lesions on spinal cord magnetic resonance imaging could aid in an earlier and correct diagnosis.


2021 ◽  
pp. 44-47
Author(s):  
Cecilia Zivelonghi ◽  
Andrew McKeon

A 12-year-old girl sought care for subacute onset of cramping back pain, along with paresthesias in her lower limbs up to the waistline, both hands, upper back, and chest, followed by rapidly progressive (over a few hours) painful vision loss affecting initially the right eye with subsequent involvement of the left eye. She underwent neuroophthalmologic evaluation and was diagnosed with bilateral optic neuritis. A positive Lhermitte sign was also present. The patient was tested for aquaporin-4-immunoglobulin G autoantibodies, which were positive in both serum and cerebrospinal fluid. A diagnosis of aquaporin-4-immunoglobulin G–positive neuromyelitis optica was made. The patient was treated with rituximab (anti-CD20 monoclonal antibody) and became episode-free, with no further accumulation of disability. The discovery of aquaporin-4-immunoglobulin G in 2004 has permitted the distinction of neuromyelitis optica spectrum disorder from other inflammatory central nervous system disorders. Aquaporin-4-immunoglobulin G represents a highly specific biomarker for neuromyelitis optica (almost 100% using molecular-based techniques), with sensitivity of approximately 80%. According to the most recent diagnostic criteria published in 2015, a diagnosis of neuromyelitis optica spectrum disorder can also be made for patients who are aquaporin-4-immunoglobulin G seronegative by any testing method, regardless of assay sensitivity, provided that more stringent clinical and radiologic requirements are met. Serial testing is recommended for these patients because late seroconversion has been described up to 4 years after the first episode.


2017 ◽  
Vol 1859 (8) ◽  
pp. 1326-1334 ◽  
Author(s):  
Domenico Alberga ◽  
Daniela Trisciuzzi ◽  
Gianluca Lattanzi ◽  
Jeffrey L. Bennett ◽  
Alan S. Verkman ◽  
...  

2005 ◽  
Vol 202 (4) ◽  
pp. 473-477 ◽  
Author(s):  
Vanda A. Lennon ◽  
Thomas J. Kryzer ◽  
Sean J. Pittock ◽  
A.S. Verkman ◽  
Shannon R. Hinson

Neuromyelitis optica (NMO) is an inflammatory demyelinating disease that selectively affects optic nerves and spinal cord. It is considered a severe variant of multiple sclerosis (MS), and frequently is misdiagnosed as MS, but prognosis and optimal treatments differ. A serum immunoglobulin G autoantibody (NMO-IgG) serves as a specific marker for NMO. Here we show that NMO-IgG binds selectively to the aquaporin-4 water channel, a component of the dystroglycan protein complex located in astrocytic foot processes at the blood-brain barrier. NMO may represent the first example of a novel class of autoimmune channelopathy.


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