Evidence map›Paper›PMID 34168058›Full record

ArticleNeurology(R) neuroimmunology & neuroinflammation2021

Molecular Level Characterization of Circulating Aquaporin-4 Antibodies in Neuromyelitis Optica Spectrum Disorder.

Jie Li, Sam A Bazzi, Florian Schmitz, Hidetaka Tanno, Jonathan R McDaniel, Chang-Han Lee, Chaitanya Joshi, Jin Eyun Kim, Nancy Monson, Benjamin M Greenberg and 3 more

Open access · goldAbstract read
In one paragraph

Article in Neurology(R) neuroimmunology & neuroinflammation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
2.3field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 25 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 1 institution in 2 countries.

Jie LiFrom the Department of Chemical Engineering (J.L., H.T., J.R.M., C.-H.L.), University of Texas at Austin, TX; Department of Neurology (S.A.B., E.M.), Dell Medical School, University of Texas at Austin, TX; Department of Chemistry & Molecular Biology (F.S., K.H.), University of Gothenburg, Sweden; Department of Neurology and Neurotherapeutics (C.J., N.M., B.M.G.), University of Texas Southwestern Medical Center, Dallas, TX; Department of Biomedical Engineering (J.E.K.), University of Texas at Austin, TX; and Department of Molecular Biosciences (G.C.I.), University of Texas at Austin, TX.
Sam A BazziFrom the Department of Chemical Engineering (J.L., H.T., J.R.M., C.-H.L.), University of Texas at Austin, TX; Department of Neurology (S.A.B., E.M.), Dell Medical School, University of Texas at Austin, TX; Department of Chemistry & Molecular Biology (F.S., K.H.), University of Gothenburg, Sweden; Department of Neurology and Neurotherapeutics (C.J., N.M., B.M.G.), University of Texas Southwestern Medical Center, Dallas, TX; Department of Biomedical Engineering (J.E.K.), University of Texas at Austin, TX; and Department of Molecular Biosciences (G.C.I.), University of Texas at Austin, TX.
Florian SchmitzFrom the Department of Chemical Engineering (J.L., H.T., J.R.M., C.-H.L.), University of Texas at Austin, TX; Department of Neurology (S.A.B., E.M.), Dell Medical School, University of Texas at Austin, TX; Department of Chemistry & Molecular Biology (F.S., K.H.), University of Gothenburg, Sweden; Department of Neurology and Neurotherapeutics (C.J., N.M., B.M.G.), University of Texas Southwestern Medical Center, Dallas, TX; Department of Biomedical Engineering (J.E.K.), University of Texas at Austin, TX; and Department of Molecular Biosciences (G.C.I.), University of Texas at Austin, TX.
Hidetaka TannoFrom the Department of Chemical Engineering (J.L., H.T., J.R.M., C.-H.L.), University of Texas at Austin, TX; Department of Neurology (S.A.B., E.M.), Dell Medical School, University of Texas at Austin, TX; Department of Chemistry & Molecular Biology (F.S., K.H.), University of Gothenburg, Sweden; Department of Neurology and Neurotherapeutics (C.J., N.M., B.M.G.), University of Texas Southwestern Medical Center, Dallas, TX; Department of Biomedical Engineering (J.E.K.), University of Texas at Austin, TX; and Department of Molecular Biosciences (G.C.I.), University of Texas at Austin, TX.
Jonathan R McDanielFrom the Department of Chemical Engineering (J.L., H.T., J.R.M., C.-H.L.), University of Texas at Austin, TX; Department of Neurology (S.A.B., E.M.), Dell Medical School, University of Texas at Austin, TX; Department of Chemistry & Molecular Biology (F.S., K.H.), University of Gothenburg, Sweden; Department of Neurology and Neurotherapeutics (C.J., N.M., B.M.G.), University of Texas Southwestern Medical Center, Dallas, TX; Department of Biomedical Engineering (J.E.K.), University of Texas at Austin, TX; and Department of Molecular Biosciences (G.C.I.), University of Texas at Austin, TX.ORCID 0000-0001-8575-3535
Chang-Han LeeFrom the Department of Chemical Engineering (J.L., H.T., J.R.M., C.-H.L.), University of Texas at Austin, TX; Department of Neurology (S.A.B., E.M.), Dell Medical School, University of Texas at Austin, TX; Department of Chemistry & Molecular Biology (F.S., K.H.), University of Gothenburg, Sweden; Department of Neurology and Neurotherapeutics (C.J., N.M., B.M.G.), University of Texas Southwestern Medical Center, Dallas, TX; Department of Biomedical Engineering (J.E.K.), University of Texas at Austin, TX; and Department of Molecular Biosciences (G.C.I.), University of Texas at Austin, TX.
Chaitanya JoshiFrom the Department of Chemical Engineering (J.L., H.T., J.R.M., C.-H.L.), University of Texas at Austin, TX; Department of Neurology (S.A.B., E.M.), Dell Medical School, University of Texas at Austin, TX; Department of Chemistry & Molecular Biology (F.S., K.H.), University of Gothenburg, Sweden; Department of Neurology and Neurotherapeutics (C.J., N.M., B.M.G.), University of Texas Southwestern Medical Center, Dallas, TX; Department of Biomedical Engineering (J.E.K.), University of Texas at Austin, TX; and Department of Molecular Biosciences (G.C.I.), University of Texas at Austin, TX.
Jin Eyun KimFrom the Department of Chemical Engineering (J.L., H.T., J.R.M., C.-H.L.), University of Texas at Austin, TX; Department of Neurology (S.A.B., E.M.), Dell Medical School, University of Texas at Austin, TX; Department of Chemistry & Molecular Biology (F.S., K.H.), University of Gothenburg, Sweden; Department of Neurology and Neurotherapeutics (C.J., N.M., B.M.G.), University of Texas Southwestern Medical Center, Dallas, TX; Department of Biomedical Engineering (J.E.K.), University of Texas at Austin, TX; and Department of Molecular Biosciences (G.C.I.), University of Texas at Austin, TX.
Nancy MonsonFrom the Department of Chemical Engineering (J.L., H.T., J.R.M., C.-H.L.), University of Texas at Austin, TX; Department of Neurology (S.A.B., E.M.), Dell Medical School, University of Texas at Austin, TX; Department of Chemistry & Molecular Biology (F.S., K.H.), University of Gothenburg, Sweden; Department of Neurology and Neurotherapeutics (C.J., N.M., B.M.G.), University of Texas Southwestern Medical Center, Dallas, TX; Department of Biomedical Engineering (J.E.K.), University of Texas at Austin, TX; and Department of Molecular Biosciences (G.C.I.), University of Texas at Austin, TX.
Benjamin M GreenbergFrom the Department of Chemical Engineering (J.L., H.T., J.R.M., C.-H.L.), University of Texas at Austin, TX; Department of Neurology (S.A.B., E.M.), Dell Medical School, University of Texas at Austin, TX; Department of Chemistry & Molecular Biology (F.S., K.H.), University of Gothenburg, Sweden; Department of Neurology and Neurotherapeutics (C.J., N.M., B.M.G.), University of Texas Southwestern Medical Center, Dallas, TX; Department of Biomedical Engineering (J.E.K.), University of Texas at Austin, TX; and Department of Molecular Biosciences (G.C.I.), University of Texas at Austin, TX.
Kristina HedfalkFrom the Department of Chemical Engineering (J.L., H.T., J.R.M., C.-H.L.), University of Texas at Austin, TX; Department of Neurology (S.A.B., E.M.), Dell Medical School, University of Texas at Austin, TX; Department of Chemistry & Molecular Biology (F.S., K.H.), University of Gothenburg, Sweden; Department of Neurology and Neurotherapeutics (C.J., N.M., B.M.G.), University of Texas Southwestern Medical Center, Dallas, TX; Department of Biomedical Engineering (J.E.K.), University of Texas at Austin, TX; and Department of Molecular Biosciences (G.C.I.), University of Texas at Austin, TX.
Esther MelamedFrom the Department of Chemical Engineering (J.L., H.T., J.R.M., C.-H.L.), University of Texas at Austin, TX; Department of Neurology (S.A.B., E.M.), Dell Medical School, University of Texas at Austin, TX; Department of Chemistry & Molecular Biology (F.S., K.H.), University of Gothenburg, Sweden; Department of Neurology and Neurotherapeutics (C.J., N.M., B.M.G.), University of Texas Southwestern Medical Center, Dallas, TX; Department of Biomedical Engineering (J.E.K.), University of Texas at Austin, TX; and Department of Molecular Biosciences (G.C.I.), University of Texas at Austin, TX.
Gregory C IppolitoFrom the Department of Chemical Engineering (J.L., H.T., J.R.M., C.-H.L.), University of Texas at Austin, TX; Department of Neurology (S.A.B., E.M.), Dell Medical School, University of Texas at Austin, TX; Department of Chemistry & Molecular Biology (F.S., K.H.), University of Gothenburg, Sweden; Department of Neurology and Neurotherapeutics (C.J., N.M., B.M.G.), University of Texas Southwestern Medical Center, Dallas, TX; Department of Biomedical Engineering (J.E.K.), University of Texas at Austin, TX; and Department of Molecular Biosciences (G.C.I.), University of Texas at Austin, TX. gci@utexas.edu esther.melamed@austin.utexas.edu.
The University of Texas at Austin · US

Funding

Contribution of plasmablasts in the conversion of transverse myelitis to multiple sclerosisR01NS102417 · NINDS · UT SOUTHWESTERN MEDICAL CENTER · PI MONSON, NANCY L · 2018 to 2022
$2.8M
Alcohol's Impact on the Gut-Brain Axis in a Mouse Model of Multiple SclerosisK08AA027837 · NIAAA · UNIVERSITY OF TEXAS AT AUSTIN · PI MELAMED, ESTHER · 2020 to 2024
$971k
NIAAA NIH HHS K08 AA027837NINDS NIH HHS R01 NS102417
6 · The paper itself

Abstract

objectiveTo determine whether distinct aquaporin-4 (AQP4)-IgG lineages play a role in neuromyelitis optica spectrum disorder (NMOSD) pathogenesis, we profiled the AQP4-IgG polyclonal serum repertoire and identified, quantified, and functionally characterized distinct AQP4-IgG lineages circulating in 2 patients with NMOSD.

methodsWe combined high-throughput sequencing and quantitative immunoproteomics to simultaneously determine the constituents of both the B-cell receptor (BCR) and the serologic (IgG) anti-AQP4 antibody repertoires in the peripheral blood of patients with NMOSD. The monoclonal antibodies identified by this platform were recombinantly expressed and functionally characterized in vitro.

resultsMultiple antibody lineages comprise serum AQP4-IgG repertoires. Their distribution, however, can be strikingly different in polarization (polyclonal vs pauciclonal). Among the 4 serum AQP4-IgG monoclonal antibodies we identified in 2 patients, 3 induced complement-dependent cytotoxicity in a model mammalian cell line (

conclusionsThe composition and polarization of AQP4-IgG antibody repertoires may play an important role in NMOSD pathogenesis and clinical presentation. Here, we present a means of coupling both cellular (BCR) and serologic (IgG) antibody repertoire analysis, which has not previously been performed in NMOSD. Our analysis could be applied in the future to clinical management of patients with NMOSD to monitor disease activity over time as well as applied to other autoimmune diseases to facilitate a deeper understanding of disease pathogenesis relative to autoantibody clones.

Indexed as

AntibodiesAquaporin 4FemaleHigh-Throughput Nucleotide SequencingHumansMaleMiddle AgedNeuromyelitis OpticaProteomicsAntibodiesAQP4 protein, humanAquaporin 4

Identifiers

PMID34168058
PMCPMC8225010
OpenAlexW3173601914

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.