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

Antibodies / blood Aquaporin 4 / blood Female High-Throughput Nucleotide Sequencing Humans Male Middle Aged Neuromyelitis Optica / blood Proteomics

Journal

Neurology(R) neuroimmunology & neuroinflammation
ISSN: 2332-7812
Titre abrégé: Neurol Neuroimmunol Neuroinflamm
Pays: United States
ID NLM: 101636388

Informations de publication

Date de publication:
07 2021
Historique:
received: 01 10 2020
accepted: 27 04 2021
entrez: 25 6 2021
pubmed: 26 6 2021
medline: 1 3 2022
Statut: epublish

Résumé

To 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. We 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. Multiple 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 ( The 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.

Identifiants

DOI: 10.1212/NXI.0000000000001034 PMID: 34168058 PMC: PMC8225010
pubmed: 34168058
pii: 8/5/e1034
doi: 10.1212/NXI.0000000000001034
pmc: PMC8225010
pii:
doi:

Substances chimiques

AQP4 protein, human 0
Antibodies 0
Aquaporin 4 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : NIAAA NIH HHS
ID : K08 AA027837
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS102417
Pays : United States

Informations de copyright

Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Références

Neurology. 2013 Oct 1;81(14):1197-204
pubmed: 23997151
Neurol Neuroimmunol Neuroinflamm. 2015 Jun 18;2(4):e121
pubmed: 26140280
Sci Adv. 2020 Apr 22;6(17):eaay9093
pubmed: 32426460
Ann Neurol. 2009 Nov;66(5):617-29
pubmed: 19938104
J Clin Invest. 2019 Apr 8;129(5):2000-2013
pubmed: 30958797
Acta Neuropathol. 2013 Jun;125(6):829-40
pubmed: 23677375
Nat Med. 2016 Dec;22(12):1456-1464
pubmed: 27820605
Acta Neuropathol. 2017 Jan;133(1):43-60
pubmed: 27730299
Ann Clin Transl Neurol. 2017 May 09;4(6):369-380
pubmed: 28589164
Brain Pathol. 2013 Nov;23(6):661-83
pubmed: 24118483
J Exp Med. 2005 Aug 15;202(4):473-7
pubmed: 16087714
Bioinformatics. 2014 Aug 1;30(15):2114-20
pubmed: 24695404
Anal Chem. 2014 May 20;86(10):4758-66
pubmed: 24684310
PLoS One. 2013 Dec 10;8(12):e83036
pubmed: 24340077
Neurology. 2015 Jul 14;85(2):177-89
pubmed: 26092914
Neurol Neuroimmunol Neuroinflamm. 2015 Jan 22;2(1):e62
pubmed: 25635259
Acta Neuropathol Commun. 2019 Jul 11;7(1):112
pubmed: 31296268
Mol Membr Biol. 2011 Sep;28(6):398-411
pubmed: 21770695
Nat Methods. 2015 May;12(5):380-1
pubmed: 25924071
Protein Eng Des Sel. 2010 Apr;23(4):155-9
pubmed: 20130105
J Biol Chem. 2015 May 8;290(19):12123-34
pubmed: 25792738
J Neuroophthalmol. 2017 Sep;37(3):291-299
pubmed: 28410278
J Biol Chem. 2012 Apr 20;287(17):13829-39
pubmed: 22393049
Neurol Neuroimmunol Neuroinflamm. 2015 Jul 23;2(4):e134
pubmed: 26236760
J Neuroophthalmol. 2016 Sep;36(3):238-45
pubmed: 27529327
Cancer Immunol Immunother. 2018 May;67(5):729-738
pubmed: 29427082
Proc Natl Acad Sci U S A. 2014 Feb 11;111(6):2259-64
pubmed: 24469811
J Biol Chem. 1996 Mar 1;271(9):4577-80
pubmed: 8617713
Neurology. 2016 May 10;86(19):1772-9
pubmed: 27164713
Neuroscience. 2010 Jul 28;168(4):1009-18
pubmed: 19699271
J Cell Sci. 2012 Sep 15;125(Pt 18):4405-12
pubmed: 22718347
J Neuroinflammation. 2015 Jan 28;12:19
pubmed: 25626447
Clin Dev Immunol. 2013;2013:146219
pubmed: 23710199
Clin Exp Neuroimmunol. 2014 Oct;5(3):290-303
pubmed: 27840658
Immunity. 2019 Jun 18;50(6):1530-1541.e8
pubmed: 31216462
Cells. 2019 Jan 27;8(2):
pubmed: 30691235
J Biol Chem. 2009 Dec 18;284(51):35850-60
pubmed: 19843522
J Neuroinflammation. 2018 Oct 22;15(1):294
pubmed: 30348195
Nat Protoc. 2016 Mar;11(3):429-42
pubmed: 26844430
Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):10908-12
pubmed: 8855281

Auteurs

Jie Li (J)

From 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 Bazzi (SA)

From 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 Schmitz (F)

From 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 Tanno (H)

From 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 McDaniel (JR)

From 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 Lee (CH)

From 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 Joshi (C)

From 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 Kim (JE)

From 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 Monson (N)

From 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 Greenberg (BM)

From 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 Hedfalk (K)

From 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 Melamed (E)

From 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 Ippolito (GC)

From 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.

Articles similaires

Comprehensive comparative analysis and development of molecular markers for Lasianthus species based on complete chloroplast genome sequences.

Yue Zhang, Meifang Song, Deying Tang et al.
1.00
Genome, Chloroplast Phylogeny Genetic Markers Base Composition High-Throughput Nucleotide Sequencing

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Molecular Level Characterization of...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Protéines de transport membranaire › Canaux ioniques › Porines › Aquaporines › Aquaporine-4 › Molecular Level Characterization of...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de séquence › Séquençage nucléotidique à haut débit › Molecular Level Characterization of...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Molecular Level Characterization of...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › Molecular Level Characterization of...
questionsmedicales.fr › Maladies du système immunitaire › Maladies auto-immunes › Maladies auto-immunes du système nerveux › Maladies démyélinisantes auto-immunes du SNC › Neuromyélite optique › Molecular Level Characterization of...
questionsmedicales.fr › Disciplines des sciences naturelles › Chimie › Biochimie › Protéomique › Molecular Level Characterization of...