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Detection of anti-aquaporin-4 autoantibodies in the sera of Chinese neuromyelitis optica patients

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Neural Regeneration Research 2013年第8期8卷 708-713页

作者： Miao Li Weiheng Su Jie Wang Francesco Pisani Antonio Frigeri Tonghui Ma Membrane Channel Research Laboratory Northeast Normal University Department of Neurosurgery China-Japan Union HospitalJilin University National Engineering Laboratory for AIDS Vaccine College of Life ScienceJilin University Department of General and Environmental Physiology and Centre of Excellence in Comparative Genomics (CEGBA) University of Bari

In this study, we recruited 10 neuromyelitis optica patients, two multiple sclerosis patients and two myelitis patients. Chinese hamster lung fibroblast （V79） cells transfected with a human aquaporin-4-mCherry fusion protein gene were used to detect anti-aquaporin-4 antibody in neuromyelitis optica patient sera by immunofluorescence. Anti-aquaporin-4 autoantibody was stably detected by immunofluorescence in neuromyelitis optica patient sera exclusively. The sensitivity of the assay for neuromyelitis optica was 90% and the specificity for neuromyelitis optica was 100%. The anti-aquaporin-4 antibody titers in sera were tested with serial dilutions until the signal disappeared. A positive correlation was detected between Expanded Disability Status Scale scores and serum anti-aquaporin-4 antibody titers. The anti-aquaporin-4 antibody assay is highly sensitive and specific in the sera of Chinese neuromyelitis optica patients. Detection of aquaporin-4 autoantibody is important for the diagnosis and treatment of neuromyelitis optica.

关键词： neural regeneration neurodegenerative diseases neuromyelitis optica multiple sclerosis aquaporin-4 autoimmune disease autoantibody immunofluorescence Expanded Disability StatusScale grants-supported paper photographs-containing paper neuroregeneration

No association between identified multiple sclerosis non-MHC risk loci and neuromyelitis optica

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Neuroscience Bulletin 2014年第6期30卷 1036-1044页

作者： Qi-Bing Liu Zhen-Xin Li Gui-Xian Zhao Hai Yu Zhi-Ying Wu Department of Neurology and Institute of Neurology Huashan HospitalInstitutes of Brain Science and State Key Laboratory of Medical NeurobiologyShanghai Medical CollegeFudan University Department of Neurology and Institute of Neurology First Affiliated HospitalFujian Medical University

neuromyelitis optica（NMO） and multiple sclerosis（ M S） a r e b o t h a u t o i m m u n e i n f l a m m a t o r y a n d demyelinating disorders of the central nervous system. Recently, more than 50 MS-susceptibility single-nucleotide polymorphisms（SNPs） have been detected outside the major histocompatibility complex（MHC） region. In this study, we aimed to evaluate the association of these identified non-MHC MS risk loci with Chinese patients with NMO. Thirtyfive non-MHC SNPs were selected and genotyped by matrix-assisted laser desorption/ionization timeof-fl ight mass spectrometry（MALDI-TOF MS） in 110 NMO patients and 332 controls from southeastern China. Among the 35 SNPs, only one, rs1800693 in the TNFRSF1 A locus, was nominally associated with NMO（P = 0.045, OR = 1.550, 95% CI = 1.007 – 2.384）. However, none of the 35 SNPs was associated with NMO after Bonferroni correction. Our results showed no association between these identified non-MHC MS risk loci and NMO, suggesting there are genetic differences in the etiology of NMO and MS.

关键词： neuromyelitis optica major histocompatibility complex association Chinese

Biomarkers for neuromyelitis optica:a visual analysis of emerging research trends

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Neural Regeneration Research 2024年第12期19卷 2735-2749页

作者： Xiangjun Li Jiandong Zhang Siqi Zhang Shengling Shi Yi’an Lu Ying Leng Chunyan Li Department of Ophthalmology Affiliated Hospital of Beihua UniversityJilinJilin ProvinceChina Department of Ophthalmology Changchun Bright Eye HospitalChangchunJilin ProvinceChina Departemt of Endocrinology Affiliated Hospital of Beihua UniversityJilinJilin ProvinceChina

neuromyelitis optica is an inflammatory demyelinating disease of the central nervous system that differs from multiple *** the past 20 years,the search for biomarke rs for neuromyelitis optica has been ***,we used a bibliometric approach to analyze the main research focus in the field of biomarkers for neuromyelitis *** in this area is consistently increasing,with China and the United States leading the way on the number of studies *** Mayo Clinic is a highly reputable institution in the United States,and was identified as the most authoritative institution in this ***,Professor Wingerchuk from the Mayo Clinic was the most authoritative expe rt in this *** analysis revealed that the terms "neuro myelitis optica"(261 times), "multiple sclerosis"(220 times), "neuromyelitis optica spectrum disorder"(132 times), "aquaporin4"(99 times),and "optical neuritis"(87 times) were the most frequently used keywords in literature related to this *** analysis of the classical literature showed that the majority of publications provide conclusive research evidence supporting the use of aquaporin-4-IgG and neuromyelitis optica-IgG to effectively diagnose and differentiate neuromyelitis optica from multiple ***,aquaporin-4-IgG has emerged as a highly specific diagnostic biomarker for neuromyelitis optica spectrum *** oligodendrocyte glycoprotein-IgG is a diagnostic biomarke r for myelin oligodendrocyte glycoprotein antibody-associated *** biomarkers for neuromyelitis optica in clude cerebrospinal fluid immunological biomarkers such as glial fibrillary acidic protein,serum astrocyte damage biomarkers like FAM19A5,serum albumin,and gammaaminobutyric *** latest prospective clinical trials are exploring the potential of these *** results indicate that glial fibrillary acidic protein is emerging as a promising candidate biomarker for neuromyelit

关键词： aquaporin-4 autoantibody multiple sclerosis myelin oligodendrocyte glycoprotein antibody-associated disease neuromyelitis optica neuromyelitis optica spectrum disorder optical coherence tomography

Autologous mesenchymal stem cells applied on the pressure ulcers had produced a surprising outcome in a severe case of neuromyelitis optica

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Neural Regeneration Research 2015年第11期10卷 1841-1845页

作者： Adriana Octaviana Dulamea Mirela-Patricia Sirbu-Boeti Coralia Bleotu Denisa Dragu Lucia Moldovan Ioana Lupescu Giancarlo Comi U.M.F.Carol Davila 8 Bulevardul Eroii Sanitari Department of Neurology Fundeni Clinical Institute National Virology Institute Stefan S.Nicolau National Institute of Research and Development for Biological Sciences Universita Vita-Salute San Raffaele

Recent studies provided evidence that mesenchymal stem cells（MSCs） have regenerative potential in cutaneous repair and profound immunomodulatory properties making them a candidate for therapy of neuroimmunologic diseases. neuromyelitis optica（NMO） is an autoimmune, demyelinating central nervous system disorder characterized by a longitudinally extensive spinal cord lesion. A 46-year-old male diagnosed with NMO had relapses with paraplegia despite treatment and developed two stage IV pressure ulcers（PUs） on his legs. The patient consented for local application of autologous MSCs on PUs. MSCs isolated from the patient＇s bone marrow aspirate were multiplied in vitro during three passages and embedded in a tridimensional collagen-rich matrix which was applied on the PUs. Eight days after MSCs application the patient showed a progressive healing of PUs and improvement of disability. Two months later the patient was able to walk 20 m with bilateral assistance and one year later he started to walk without assistance. For 76 months the patient had no relapse and no adverse event was reported. The original method of local application of autologous BM-MSCs contributed to healing of PUs. For 6 years the patient was free of relapses and showed an improvement of disability. The association of cutaneous repair, sustained remission of NMO and improvement of disability might be explained by a promotion/optimization of recovery mechanisms in the central nervous system even if alternative hypothesis should be considered. Further studies are needed to assess the safety and efficacy of mesenchymal stem cells in NMO treatment.

关键词： neuromyelitis optica Devic's syndrome mesenchymal stem cells multiple sclerosis pressure ulcers

Seropositivity rates of water channel protein 4 antibodies compared between a cell-based immunofluorescence assay and an enzyme-linked immunosorbent assay in neuromyelitis optica patients

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Neural Regeneration Research 2011年第32期6卷 2490-2494页

作者： Xiaoli Wu Zhangyuan Liao Jing Ye Huiqing Dong ChaodongWang Piu Chan Department of Neurology and Key Laboratory Ministry of Education on Neurodegenerative Diseases Xuanwu Hospital of Capital MedicalUniversity Beijing 100053 China Department of Neurology Xuanwu Hospital of Capital Medical University Beijing 100053 China

A total of 66 samples （from 27 cases with neuromyelitis optica, 26 cases with multiple sclerosis, aa 13 cases with optic neuritis） were tested for aquaporin-4 antibody by a cell-based immunofluorescence assay and an enzyme-linked immunosorbent assay. The sensitivities and specificities of the two assays were similar. We further analyzed an additional 68 patients and 93 healthy controls using the enzyme-linked immunosorbent assay. A Kappa test showed good consistency between the two methods in terms of detection of anti-aquaporin-4 antibody in the se of neuromyelitis optica patients. No significant correlations were identified with onset age or disea duration, suggesting that aquaporin-4 antibody is a good marker for neuromyelitis optica. The enzyme-linked immunosorbent assay can be used for quantifying aquaporin-4 antibody concentrations and may be useful to dynamically monitor changes in the levels of aquaporin-4 antibody during disease duration.

关键词： neuromyelitis optica cell-based immunofluorescence assay anti-aquaporin 4 antibody enzyme-linked immunosorbent assay long and extended spinal cord lesions neural regeneration

Macular changes of neuromyelitis optica through spectral-domain optical coherence tomography

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International Journal of Ophthalmology(English edition) 2016年第11期9卷 1638-1645页

作者： Lu Cheng Jing Wang Xu He Xun Xu Zhen-Fen Ling Department of Ophthalmology Shanghai Jiao Tong University Affiliated Shanghai First People's HospitalShanghai 20080 China Shanghai Key Laboratory of Fundus Disease Shanghai 20080 China Case Western Reserve University School of Medicine Cleveland Ohio 44106 USA Department of Neurology Shanghai Jiao Tong University Affiliated Shanghai First People's Hospital Shanghai 20080China

AIM： To evaluate the thickness of the retinal layers in the macula using spectral-domain optical coherence tomography（SD-OCT） in patients with neuromyelitis optica（NMO）. METHODS： Spectralis SD-OCT, utilizing automated macular layer segmentation, was performed in 26 NMO patients and 26 healthy controls. Visual function including visual field tests and pattern visual evoked potential were recorded in study ***： Forty-one eyes from 26 NMO patients and52 eyes from 26 age- and sex-matched healthy controls were included. Besides total macular volume, peri-paipillary retinal nerve fiber layer（RNFL） thickness, the thickness of macular RNFL, ganglion cell layer（GCL） and inner plexiform layer（IPL） were also significantly reduced in NMO patients compared to those inhealthy controls（P 〈0.000）. No differences were found in the thickness of macular inner nuclear layer（INL）, outer plexiform layer（OPL）, and outer nuclear layer（ONL） between the two groups. Reversely, the outer retinal layer（ORL） was shown to be thicker in NMO than controls（P 〈0.05）.Compared with the peri-papillary RNFL thickness, the GCL thickness was demonstrated to correlate with visual function ***： The study provides in vivo evidence of retinal neural loss in NMO patients and demonstrates abetter structure-function correlation between retinal ganglion cell and visual function than peri-papillary RNFL does. In addition, no evidence of primary neural damage is found. Besides, the photoreceptor cells and retinal pigments epithelial（RPE） cells presumably proliferated in compensation in NMO after retinal neural loss.

关键词： neuromyelitis optica optical coherencetomography macular layer thickness ganglion cell loss

Higher frequency of brain abnormalities in neuromyelitis optica spectrum disorder patients without primary Sjogren's syndrome

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Neural Regeneration Research 2016年第10期11卷 1633-1637页

作者： Li-na Gu Min Zhang Hui Zhu Jing-yao Liu Department of Intensive Care Unit First Hospital Jilin University Changchun Jilin Province China Department of Acupuncture and Moxibustion Changchun University of Chinese Medicine Changchun Jilin Province China Department of Neurology First Hospital Jilin University Changchun Jilin Province China

neuromyelitis optica spectrum disorder often co-exists with primary Sjogreffs syndrome. We compared the clinical features of 16 neuro- myelitis optica spectrum disorder patients with （n = 6） or without primary Sjogreffs syndrome （n = 10）. All patients underwent extensive clinical, laboratory, and MRI evaluations. There were no statistical differences in demographics or first neurological involvement at onset between neuromyelitis optica spectrum disorder patients with and without primary Sjogren＇s syndrome. The laboratory findings of cerebrospinal fluid oligoclonal banding, serum C-reactive protein, antinudear autoantibody, anti-Sjogren＇s-syndrome-related antigen A an- tibodies, anti-Sjogren＇s-syndrome-related antigen B antibodies, and anti-Sm antibodies were significantly higher in patients with primary Sjogren＇s syndrome than those without. Anti-aquaporin 4 antibodies were detectable in 67% （4/6） of patients with primary Sjogren＇s syndrome and in 60% （6/10） of patients without primary Sj6gren＇s syndrome. More brain abnormalities were observed in patients without primary Sj6gren＇s syndrome than in those with primary Sj6gren＇s syndrome. Segments lesions （〉 3 centrum） were noted in 50% （5/10） of patients without primary Sj6gren＇s syndrome and in 67% （4/6） of patients with primary Sjogren＇s syndrome. These findings indicate that the clinical characteristics of neuromyelitis optica spectrum disorder patients with and without primary Sjogren＇s syndrome are similar. However, neu- romyelitis optica spectrum disorder patients without primary Sjogreffs syndrome have a high frequency of brain abnormalities.

关键词： nerve regeneration neuromyelitis optica primary Sjogren's syndrome neuromyelitis optica spectrum disorder xerostomiaxerophthalmia neurological involvements magnetic resonance imaging anti-aquaporin 4 neural regeneration

neuromyelitis optica Revealed by Headache in a Child: A Case Report

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Open Journal of Pediatrics 2023年第3期13卷 432-436页

作者： Amal Hamami Maria Rkain Madiha Benhachem Ayyad Ghannam Aziza Elouali Abdeladim Babakhoua Department of Pediatrics Mohamed VI University Hospital Center Mohamed 1 University Oujda Oujda Morocco

Devic’s neuromyelitis optica (NMO) is a rare inflammatory disease of the central nervous system that results in optic neuropathy and myelitis. Optic neuritis represents the mode of entry into the disease in more than two thirds of cases. It is a rare entity in children. There is no effective treatment at present, but some molecules can be used, such as corticosteroids, immunosuppressants and plasma exchange. The prognosis in children is generally favorable. Devic’s neuromyelitis is a condition of unknown etiopathogeny which is functionally critical and requires early and appropriate treatment. We report the case of a 12-year-old girl who presented to emergency with a headache and decreased visual acuity, whose investigations led to the diagnosis of Devic’s neuromyelitis optica.

关键词： neuromyelitis optica Devic Syndrome Child

Variants of Interleukin-7/Interleukin-7 Receptor Alpha are Associated with Both neuromyelitis optica and Multiple Sclerosis Among Chinese Han Population in Southeastern China

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Chinese Medical Journal 2015年第22期128卷 3062-3068页

作者： Jing-Cong Zhuang Lei Wu Mei-Zhen Qian Ping-Ping Cai Qi-Bing Liu Gui-Xian Zhao Zhen-Xin Li Zhi-Ying Wu Department of Neurology Institute of Neurology First Affiliated Hospital Fujian Medical University Fuzhou Fujian 350004 China Department of Neurology Research Center of Neurology Second Affiliated Hospital The Collaborative Innovation Center for Brain Science Zhejiang University School of Medicine Hangzhou Zhejiang 310009 China Department of Neurology Institute of Neurology Huashan Hospital Shanghai Medical College Fudan University Shanghai 200040 China

Background： neuromyelitis optica （NMO） and multiple sclerosis （MS） are autoimmune demyelinating diseases of the central nerve system, lnterleukin-7 （IL-7） and interleukin-7 receptor alpha （IL-7Rα） were proved to be important in the pathogenesis of both diseases because of the roles they played in the differentiations of autoimmune lymphocytes. The variants of both genes had been identified to be associated with MS susceptibility in Caucasian, Japanese and Korean populations. However, the association of these variants with NMO and MS has not been well studied in Chinese Southeastern Han population. Here, we aimed to evaluate the association of six IL-7 variants （rsl520333, rs1545298, rs4739140, rs6993386, rs7816065, and rs2887502） and one variant of IL-7RA （rs6897932） with NMO and MS among Chinese Han population in southeastern China. Methods： Matrix-assisted laser desorption/ionization time of flight mass spectrometry （MassARRAY system） and Sanger sequencing were used to determine the variants of IL-7 and IL-7RA in 167 NMO patients, 159 MS patients and 479 healthy controls among Chinese Han population in southeastern China. Samples were excluded if the genotyping success rate 〈90%. Results： Statistical differences were observed in the genotypes of IL-7 rs1520333 in MS patients and IL-7RA rs6897932 in NMO patients, compared with healthy controls （P = 0.035 and 0.034, respectively）. There was a statistically significant difference in the genotypes of IL-7 rs2887502 between MS and NMO patients （P = 0.014）. And there were statistically significant differences in the rs6897932 genotypes （P = 0.004） and alleles （P = 0.042） between NMO-IgG positive patients and healthy controls. Conclusions： The study suggested that among Chinese Hart population in southeastern China, the variant of IL-7RA （rs6897932） was associated with NMO especially NMO-IgG positive patients while the variant of IL-7 （rs1520333） with MS patients. And the genotypic differences of IL-7 rs2887502 between M

关键词： Association lnterleukin-7/Interleukin-7 Receptor Alpha Multiple Sclerosis neuromyelitis optica Chinese Han Population