Quantitative assays for anti-aquaporin-4 antibody with subclass analysis in neuromyelitis optica

Background: To clarify the clinical relevance of anti-aquaporin-4 (anti-AQP4) antibody titers and immunoglobulin (IgG) subclass. Methods: Using a bridging enzyme-linked immunosorbent assay (ELISA), a flow cytometric assay (FCMA) and an immunofluorescence assay (IFA) for anti-AQP4 antibodies, sera from 142 patients with multiple sclerosis (MS) as defined by the McDonald criteria (2005), 29 with neuromyelitis optica (NMO) who fulfilled the 1999 criteria, 19 with recurrent and/or longitudinally extensive myelitis (RM/LM), 86 with other non-inflammatory neurological diseases (OND) and 28 healthy controls (HC) were studied. Results: Anti-AQP4 antibody positivity rates by IFA, FCMA, and ELISA were 41.4%, 51.7% and 48.3%, respectively, in NMO (1999) patients, and 0% in the OND and HC groups. Twenty-six MS patients (18.3%) were positive for the antibody; 17 met the 2006 NMO criteria, including positivity for anti-AQP4 antibody, and five had longitudinally extensive myelitis (LM). Among the cases with anti-AQP4 antibody detected by FCMA, IgG1, 2, 3, and 4 anti-AQP4 antibodies were found in 97.8%, 37.0%, 6.5% and 6.5% respectively. There was no association of either antibody positivity or level of anti-AQP4 antibody IgG subclasses with clinical parameters after adjustment of p values for multiple comparisons. Conclusions: FCMA and bridging ELISA are useful for detecting and quantifying anti-AQP4 antibodies.

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Aquaporin-4 autoimmune syndrome and anti-aquaporin-4 antibody-negative opticospinal multiple sclerosis in Japanese

Multiple Sclerosis Journal ◽

10.1177/1352458509104595 ◽

2009 ◽

Vol 15 (7) ◽

pp. 834-847 ◽

Cited By ~ 54

Author(s):

T Matsushita ◽

N Isobe ◽

T Matsuoka ◽

N Shi ◽

Y Kawano ◽

...

Keyword(s):

Multiple Sclerosis ◽

T Cell ◽

Serum Antibody ◽

Demyelinating Diseases ◽

Aquaporin 4 ◽

Immunological Parameters ◽

Antibody Positivity ◽

Antibody Titers ◽

Ifn Γ ◽

Aqp4 Antibody

Background Antibodies to aquaporin-4 (AQP4) are found in a fraction of Japanese opticospinal multiple sclerosis (OSMS) patients. However, it remains unknown whether anti-AQP4 antibody-positive and negative OSMS patients possess an identical disease. Objective The objective of the current study was to clarify immunological differences between the two groups of patients. Methods We studied the serum antibody titers against AQP4 in 191 patients with idiopathic central nervous system demyelinating diseases and clarified their relationships with immunological parameters. Results Anti-AQP4 antibody positivity rate was higher in patients with OSMS (21/58, 36.2%), idiopathic recurrent myelitis (4/17, 23.5%), and recurrent optic neuritis (7/26, 26.9%), than in conventional MS (CMS) patients (6/90, 6.7%) and patients with other diseases (0/87). Anti-AQP4 antibody titer was significantly higher in patients with SS-A/B antibodies than in those without them. Anti-AQP4 antibody-negative OSMS patients showed significantly higher CD4+IFN-γ+IL-4−T cell percentages and intracellular IFN-γ/IL-4 ratios than anti-AQP4 antibody-positive patients, anti-AQP4 antibody-negative CMS patients, and healthy controls, and CD4+IFN-γ+IL-4−T cell percentages were negatively correlated with anti-AQP4 antibody titers. Conclusion Anti-AQP4 antibody-positive patients are immunologically distinct from anti-AQP4 antibody-negative OSMS patients owing to a Th2 shift in the former group in comparison to a Th1 shift in the latter.

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Association of anti-Helicobacter pylori neutrophil-activating protein antibody response with anti-aquaporin-4 autoimmunity in Japanese patients with multiple sclerosis and neuromyelitis optica

Multiple Sclerosis Journal ◽

10.1177/1352458509348961 ◽

2009 ◽

Vol 15 (12) ◽

pp. 1411-1421 ◽

Cited By ~ 44

Author(s):

Wei Li ◽

Motozumi Minohara ◽

Hua Piao ◽

Takuya Matsushita ◽

Katsuhisa Masaki ◽

...

Keyword(s):

Multiple Sclerosis ◽

Helicobacter Pylori ◽

Neuromyelitis Optica ◽

Healthy Subjects ◽

Neurological Diseases ◽

Japanese Patients ◽

Aquaporin 4 ◽

Scale Scores ◽

H Pylori ◽

Aqp4 Antibody

There are two distinct subtypes of multiple sclerosis (MS) in Asians: opticospinal (OSMS) and conventional (CMS). OSMS has similar features to neuromyelitis optica (NMO) and half of OSMS patients have the NMO-Immunoglobulin G (IgG)/ anti-aquaporin-4 (AQP4) antibody. We reported that Helicobacter pylori (H. pylori) infection was significantly less common in CMS patients than controls. To reveal the immune responses to the H. pylori neutrophil-activating protein (HP-NAP) in Japanese MS patients, according to anti-AQP4 antibody status, sera from 162 MS patients, 37 patients with other inflammatory neurological diseases (OIND), and 85 healthy subjects were assayed for anti-H. pylori antibodies, anti-HP-NAP antibodies, and myeloperoxidase (MPO) by enzyme immunoassays. H. pylori seropositivity rates were significantly higher in anti-AQP4 antibody-positive MS/NMO (AQP4 + /MS) patients (19/27, 70.4%) than anti-AQP4 antibody-negative CMS (AQP4 — /CMS) patients (22/83, 26.5%). Among H. pylori-infected individuals, the anti-HP-NAP antibody was significantly more common in AQP4 + /MS and AQP4 — /OSMS patients than healthy subjects (36.8%, 34.6% versus 2.8%). Among the AQP4 + /MS patients, a significant positive correlation between anti-HP-NAP antibody levels and the final Kurtzke’s Expanded Disability Status Scale scores was found, and MPO levels were higher in anti-HP-NAP antibody-positive patients than anti-HP-NAP antibody-negative ones. Therefore, HP-NAP may be associated with the pathology of anti-AQP4 antibody-related neural damage in MS/NMO patients.

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Quantitative measurement of anti-aquaporin-4 antibodies by enzyme-linked immunosorbent assay using purified recombinant human aquaporin-4

Multiple Sclerosis Journal ◽

10.1177/1352458511424590 ◽

2011 ◽

Vol 18 (5) ◽

pp. 578-586 ◽

Cited By ~ 46

Author(s):

Woojun Kim ◽

Ji-Eun Lee ◽

Xue Feng Li ◽

Su-Hyun Kim ◽

Byeong-Gu Han ◽

...

Keyword(s):

High Risk ◽

Disease Activity ◽

Immunosorbent Assay ◽

Neurological Diseases ◽

Aquaporin 4 ◽

Enzyme Linked Immunosorbent Assay ◽

Specific Marker ◽

Longitudinal Measurement ◽

Longitudinal Measurements ◽

Baculovirus System

Background: Antibodies to aquaporin-4 (AQP4-Ab), known as NMO-IgG, are a sensitive and specific marker for neuromyelitis optica (NMO). Methods: To develop an enzyme-linked immunosorbent assay (ELISA) for AQP4-Ab, we expressed M23 isoform of human AQP4 in a baculovirus system, and used it as an antigen. We measured AQP4-Ab in the sera of 300 individuals: 64 with definite NMO, 31 with high-risk NMO, 105 with multiple sclerosis (MS), 57 with other neurological diseases (ONDs), and 43 healthy controls. We also performed longitudinal measurements of AQP4–Ab in 787 samples collected from 51 patients with definite or high-risk NMO. Results: AQP4-Abs were positive in 72% with definite NMO, 55% with high-risk NMO, and 4% with MS, but none of the OND patients and the healthy individuals. The longitudinal measurement showed AQP4-Ab levels correlating with disease activity. Out of 38 initially seropositive patients, 21 became seronegative under effective immunosuppressive therapy. During most relapses, the serum AQP4-Ab levels were either high or rising compared with the previous value, although rising AQP4-Ab levels did not always lead to acute exacerbation. Two of the 13 initially seronegative patients converted to seropositive following acute exacerbations. Conclusions: We established an AQP4-Ab ELISA, which could be a potential monitoring tool of disease activity.

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Transient increases in anti-aquaporin-4 antibody titers following rituximab treatment in neuromyelitis optica, in association with elevated serum BAFF levels

Journal of Clinical Neuroscience ◽

10.1016/j.jocn.2010.12.011 ◽

2011 ◽

Vol 18 (7) ◽

pp. 997-998 ◽

Cited By ~ 47

Author(s):

Ichiro Nakashima ◽

Toshiyuki Takahashi ◽

Bruce A.C. Cree ◽

Ho Jin Kim ◽

Chihiro Suzuki ◽

...

Keyword(s):

Neuromyelitis Optica ◽

Elevated Serum ◽

Aquaporin 4 ◽

Antibody Titers ◽

Aquaporin 4 Antibody

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Neuromyelitis optica and anti-aquaporin-4 antibodies measured by an enzyme-linked immunosorbent assay

Journal of Neuroimmunology ◽

10.1016/j.jneuroim.2008.03.009 ◽

2008 ◽

Vol 196 (1-2) ◽

pp. 181-187 ◽

Cited By ~ 83

Author(s):

Sei Hayakawa ◽

Masahiro Mori ◽

Akiko Okuta ◽

Akiko Kamegawa ◽

Yoshinori Fujiyoshi ◽

...

Keyword(s):

Immunosorbent Assay ◽

Neuromyelitis Optica ◽

Aquaporin 4 ◽

Enzyme Linked Immunosorbent Assay

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Reduction in Serum Aquaporin-4 Antibody Titers During Development of a Tumor-Like Brain Lesion in a Patient With Neuromyelitis Optica: A Serum Antibody–Consuming Effect?

Journal of Neuropathology & Experimental Neurology ◽

10.1097/nen.0000000000000173 ◽

2015 ◽

Vol 74 (3) ◽

pp. 194-197 ◽

Cited By ~ 3

Author(s):

Fahmy Aboulenein-Djamshidian ◽

Romana Höftberger ◽

Patrick Waters ◽

Wolfgang Krampla ◽

Hans Lassmann ◽

...

Keyword(s):

Neuromyelitis Optica ◽

Brain Lesion ◽

Serum Antibody ◽

Aquaporin 4 ◽

Antibody Titers ◽

Aquaporin 4 Antibody

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Anti-BP180 Autoantibodies Are Present in Stroke and Recognize Human Cutaneous BP180 and BP180-NC16A

10.1101/313692 ◽

2018 ◽

Cited By ~ 1

Author(s):

Yanan Wang ◽

Xuming Mao ◽

Di Wang ◽

Christoph M. Hammers ◽

Aimee S. Payne ◽

...

Keyword(s):

Clinical Outcome ◽

Neurological Diseases ◽

Current Evidence ◽

Enzyme Linked Immunosorbent Assay ◽

Healthy Controls ◽

Stroke Patients ◽

Specific Antibodies ◽

Long Duration ◽

Antibody Titers

AbstractBackgroundCurrent evidence has revealed a significant association between bullous pemphigoid (BP) and neurological diseases (ND), including stroke, but the incidence of BP autoantibodies in patients with stroke has not previously been investigated.ObjectiveOur study aims to assess BP antigen-specific antibodies in stroke patients.Methods100 patients with stroke and 100 healthy controls were randomly selected to measure anti-BP180/230 IgG autoantibodies by enzyme-linked immunosorbent assay (ELISA), salt split indirect immunofluorescence (IIF) and immunoblotting against human cutaneous BP180 and BP180-NC16A.ResultsAnti-BP180 autoantibodies were found in 14(14.0%) patients with stroke and 5(5.0 %) of controls by ELISA (p<0.05). Sera from 13(13.0%) patients with stroke and 3(3.0 %) controls reacted with 180-kDa proteins from human cutis extract (p<0.05). 11(11.0%) of stroke and 2(2.0 %) of control sera recognized the human recombinant full length BP180 and NC16A (p<0.05). The anti-BP180-positive patients were significantly younger than the negative patients in stroke (p<0.001).LimitationsLongitudinal changes in antibody titers and long-term clinical outcome for a long duration were not fully investigated.ConclusionDevelopment of anti-BP180 autoantibodies occur at a higher frequency after stroke, suggesting BP180 as a shared autoantigen in stroke with BP and providing novel insights into BP pathogenesis in aging.

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Presence of anti-Ro/SSA antibody may be associated with anti-aquaporin-4 antibody positivity in neuromyelitis optica spectrum disorder

Journal of the Neurological Sciences ◽

10.1016/j.jns.2014.11.020 ◽

2015 ◽

Vol 348 (1-2) ◽

pp. 132-135 ◽

Cited By ~ 18

Author(s):

Jae-Hyun Park ◽

Jaechun Hwang ◽

Ju-Hong Min ◽

Byoung Joon Kim ◽

Eun-Suk Kang ◽

...

Keyword(s):

Neuromyelitis Optica ◽

Spectrum Disorder ◽

Aquaporin 4 ◽

Neuromyelitis Optica Spectrum Disorder ◽

Antibody Positivity ◽

Aquaporin 4 Antibody

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Pregnancy-related relapse risk factors in women with anti-AQP4 antibody positivity and neuromyelitis optica spectrum disorder

Multiple Sclerosis Journal ◽

10.1177/1352458515583376 ◽

2016 ◽

Vol 22 (11) ◽

pp. 1413-1420 ◽

Cited By ~ 33

Author(s):

Yuko Shimizu ◽

Kazuo Fujihara ◽

Takashi Ohashi ◽

Ichiro Nakashima ◽

Kazumasa Yokoyama ◽

...

Keyword(s):

Risk Factors ◽

Multiple Sclerosis ◽

Relapse Rate ◽

Neuromyelitis Optica ◽

Spectrum Disorder ◽

Low Doses ◽

Neuromyelitis Optica Spectrum Disorder ◽

Annualized Relapse Rate ◽

Antibody Positivity ◽

Aqp4 Antibody

Background: Few reports describe the influence pregnancy has on the annualized relapse rate (ARR) in neuromyelitis optica spectrum disorder (NMOSD). Objective: To examine pregnancy-related attacks (attacks during pregnancy or within 1 year postpartum) and identify the risk factors for an attack in Japanese NMOSD patients. Methods: We retrospectively reviewed 139 Japanese women whom had aquaporin-4 (AQP4) antibody-positive NMOSD. Among the 114 patients with information, 47 women had 56 pregnancies. We compared the ARR before, during and after pregnancy. Results: Of the 47 NMOSD patients with pregnancy, 22 women (46.8%) had a pregnancy-related attack of the disease (either an onset event or a relapse). The ARR was significantly higher in the first 3 months postpartum (1.80 ± 2.04), than before the pregnancy (0.57 ± 1.16; p = 0.0043) and did not significantly decrease during pregnancy. The ARR before hospitalization and treatment was analyzable in 55 patients without pregnancy and was 1.09 ± 1.17. Among the 11 patients with onset before pregnancy, nine patients had a pregnancy-related attack with a relapse in the previous year, and their immunosuppression was discontinued or made to be at low doses; while the two patients on higher-dose therapies were relapse-free. Conclusion: In the present study, pregnancy-related attack was common in NMOSD, and unlike in multiple sclerosis, the ARR was not reduced during pregnancy. Discontinued or insufficient immunosuppression appeared to increase the risk of pregnancy-related attack.

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