Evidence map›Paper›PMID 21454592›Full record

ArticleThe Journal of biological chemistry2011

Binding affinity and specificity of neuromyelitis optica autoantibodies to aquaporin-4 M1/M23 isoforms and orthogonal arrays.

Jonathan M Crane, Chiwah Lam, Andrea Rossi, Tripta Gupta, Jeffrey L Bennett, A S Verkman

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
122citing papers in PubMed, 1 pooled it
14.1field-weighted citation impact, top 1% 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

122 citing papers in PubMed, 1 synthesis or guideline pooled it, 196 citations in OpenAlex.

  1. Pooled it
  2. Beyond Positivity: Understanding and Interpreting MOG-IgG Testing in MOGAD.Journal of clinical neurology (Seoul, Korea) · 2026
    Review
  3. Article
  4. Article
  5. Review
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Review
  12. Review
  13. Blood-Brain Barrier Disruption in Neuroimmunological Disease.International journal of molecular sciences · 2024
    Review
  14. Article
  15. Article
  16. Review
  17. Review
  18. Review
  19. Review
  20. Review

62 more citing papers are in PubMed but not listed here.

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

6 authors at 2 institutions in 1 country.

Jonathan M CraneDepartment of Medicine, University of California, San Francisco, California 94143, USA.
Chiwah Lam
Andrea Rossi
Tripta Gupta
Jeffrey L Bennett
A S Verkman
University of California, San Francisco · USUniversity of Colorado Denver · US

Funding

SynthesisP30DK072517 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VERKMAN, ALAN S · 2005 to 2022
$18.1M
Functional Role of Aquaporins in Eye PhysiologyR01EY013574 · NEI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VERKMAN, ALAN S · 2002 to 2022
$7.6M
MECHANISMS OF WATER TRANSPORT IN RENAL EPITHELIAR37DK035124 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VERKMAN, ALAN S · 1999 to 2008
$4.2M
Application of Novel Optical Methods to Cell DynamicsR37EB000415 · NIBIB · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VERKMAN, ALAN S · 2007 to 2016
$4.1M
Role of ASL and Airway Glands in CF Lung DiseaseR01HL073856 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VERKMAN, ALAN S · 2003 to 2010
$3.1M
Application of Novel Optical Methods to Cell DynamicsR01EB000415 · NIBIB · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VERKMAN, ALAN S · 2002 to 2006
$1.7M
WATER AND NON-ELECTROLYTE TRANSPORT IN RENAL VESICLESR01DK035124 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VERKMAN, ALAN S · 1986 to 2014
$1.4M
CFTR inhibitors for therapy of polycystic kidney diseaseRC1DK086125 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VERKMAN, ALAN S · 2009 to 2010
$989k
NEI NIH HHS EY13574NEI NIH HHS R01 EY013574NHLBI NIH HHS HL73856NHLBI NIH HHS R01 HL073856NIBIB NIH HHS EB00415NIBIB NIH HHS R01 EB000415NIBIB NIH HHS R37 EB000415NIDDK NIH HHS DK35124NIDDK NIH HHS DK72517NIDDK NIH HHS DK86125NIDDK NIH HHS P30 DK072517NIDDK NIH HHS R01 DK035124NIDDK NIH HHS R37 DK035124NIDDK NIH HHS RC1 DK086125
6 · The paper itself

Abstract

Autoantibodies against astrocyte water channel aquaporin-4 (AQP4) are highly specific for the neuroinflammatory disease neuromyelitis optica (NMO). We measured the binding of NMO autoantibodies to AQP4 in human astrocyte-derived U87MG cells expressing M1 and/or M23 AQP4, or M23 mutants that do not form orthogonal array of particles (OAPs). Binding affinity was quantified by two-color fluorescence ratio imaging of cells stained with NMO serum or a recombinant monoclonal NMO autoantibody (NMO-rAb), together with a C terminus anti-AQP4 antibody. NMO-rAb titrations showed binding with dissociation constants down to 44 ± 7 nm. Different NMO-rAbs and NMO patient sera showed a wide variation in NMO-IgG binding to M1 versus M23 AQP4. Differences in binding affinity rather than stoichiometry accounted for M1 versus M23 binding specificity, with consistently greater affinity of NMO-IgG binding to M23 than M1 AQP4. Binding and OAP measurements in cells expressing different M1:M23 ratios or AQP4 mutants indicated that the differential binding of NMO-IgG to M1 versus M23 was due to OAP assembly rather than to differences in the M1 versus M23 N termini. Purified Fab fragments of NMO-IgG showed similar patterns of AQP4 isoform binding, indicating that structural changes in the AQP4 epitope upon array assembly, and not bivalent cross-linking of whole IgG, result in the greater binding affinity to OAPs. Our study establishes a quantitative assay of NMO-IgG binding to AQP4 and indicates remarkable, OAP-dependent heterogeneity in NMO autoantibody binding specificity.

Indexed as

Antibody SpecificityMutationAntibodies, MonoclonalAntibody AffinityAquaporin 4AutoantibodiesCell LineHumansImmunoglobulin GNeuromyelitis OpticaAntibodies, MonoclonalAQP4 protein, humanAquaporin 4AutoantibodiesImmunoglobulin G

Identifiers

PMID21454592
PMCPMC3091256
OpenAlexW2015868606

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.