Evidence map›Paper›PMID 27304671›Full record

ArticlePloS one2016

Pathogenicity and Epitope Characteristics Do Not Differ in IgG Subclass-Switched Anti-Desmoglein 3 IgG1 and IgG4 Autoantibodies in Pemphigus Vulgaris.

Agnes S Lo, Xuming Mao, Eric M Mukherjee, Christoph T Ellebrecht, Xiaocong Yu, Marshall R Posner, Aimee S Payne, Lisa A Cavacini

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2016. 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
1.7field-weighted citation impact, top 17% 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.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Autoimmune Pemphigus: Latest Advances and Emerging Therapies.Frontiers in molecular biosciences · 2021
    Review
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  14. Review
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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

8 authors at 2 institutions in 1 country.

Agnes S LoDepartment of Medicine, Beth Israel Deaconess Medical Center, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, United States of America.
Xuming MaoDepartment of Dermatology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Eric M MukherjeeDepartment of Dermatology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Christoph T EllebrechtDepartment of Dermatology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Xiaocong YuDepartment of Medicine, Beth Israel Deaconess Medical Center, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, United States of America.
Marshall R PosnerDepartment of Medicine, Beth Israel Deaconess Medical Center, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, United States of America.
Aimee S PayneDepartment of Dermatology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Lisa A CavaciniDepartment of Medicine, Beth Israel Deaconess Medical Center, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, United States of America.ORCID http://orcid.org/0000-0003-1417-8339
Beth Israel Deaconess Medical Center · USUniversity of Pennsylvania · US

Funding

Penn Dermatology Research Training ProgramT32AR007465 · NIAMS · UNIVERSITY OF PENNSYLVANIA · PI Elizabeth Anne Grice, David Joel Margolis · 1986 to 2026
$9.0M
Understanding molecular mechanisms underlying the formation of the blue nevus andP30AR057217 · NIAMS · UNIVERSITY OF PENNSYLVANIA · PI SIMON, M. CELESTE · 2009 to 2013
$3.2M
Role of autoantibody isotype in pemphigus pathogenesisR01AR057001 · NIAMS · UNIVERSITY OF PENNSYLVANIA · PI PAYNE, AIMEE S · 2010 to 2014
$1.7M
Structure and Function of Human Pemphigus AutoantibodiesR56AR064220 · NIAMS · UNIVERSITY OF PENNSYLVANIA · PI PAYNE, AIMEE S · 2014 to 2014
$400k
Relationships Between Autoimmune IgG1 and IgG4 Repertoires in Pemphigus VulgarisF30AR065870 · NIAMS · UNIVERSITY OF PENNSYLVANIA · PI MUKHERJEE, ERIC MILAN · 2014 to 2016
$105k
NIAMS NIH HHS F30 AR065870NIAMS NIH HHS P30 AR057217NIAMS NIH HHS R01 AR057001NIAMS NIH HHS R56 AR064220NIAMS NIH HHS T32 AR007465
6 · The paper itself

Abstract

Pemphigus vulgaris (PV) is characterized by IgG1 and IgG4 autoantibodies to desmoglein (Dsg) 3, causing suprabasal blistering of skin and mucous membranes. IgG4 is the dominant autoantibody subclass in PV and correlates with disease activity, whereas IgG1 can be associated with remittent disease. It is unknown if switching the same variable region between IgG4 and IgG1 directly impacts pathogenicity. Here, we tested whether three pathogenic PV monoclonal antibodies (mAbs) from three different patients demonstrate differences in antigen affinity, epitope specificity, or pathogenicity when expressed as IgG1 or IgG4. F706 anti-Dsg3 IgG4 and F779 anti-Dsg3 IgG1, previously isolated as heterohybridomas, and Px43, a monovalent anti-Dsg3/Dsg1 IgG antibody isolated by phage display, were subcloned to obtain paired sets of IgG1 and IgG4 mAbs. Using ELISA and cell surface staining assays, F706 and F779 demonstrated similar antigen binding affinities of IgG1 and IgG4, whereas Px43 showed 3- to 8-fold higher affinity of IgG4 versus IgG1 by ELISA, but identical binding affinities to human skin, perhaps due to targeting of a quaternary epitope best displayed in tissues. All 3 mAb pairs targeted the same extracellular cadherin (EC) domain on Dsg3, caused Dsg3 internalization in primary human keratinocytes, and caused suprabasal blisters in human skin at comparable doses. We conclude that switching IgG1 and IgG4 subclasses of pathogenic PV mAbs does not directly affect their antigen binding or pathogenic properties.

Indexed as

Antibodies, MonoclonalAntibody AffinityAntibody SpecificityAutoantibodiesCells, CulturedDesmoglein 3Enzyme-Linked Immunosorbent AssayEpitope MappingEpitopesExfoliatinsHumansImmunoglobulin GKeratinocytesMicroscopy, FluorescencePemphigusSkinAntibodies, MonoclonalAutoantibodiesDesmoglein 3DSG3 protein, humanEpitopesExfoliatinsImmunoglobulin G

Identifiers

PMID27304671
PMCPMC4909199
OpenAlexW2437858587

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

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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.