Evidence map›Paper›PMID 24386452›Full record

Trial reportPloS one2013

9G4+ antibodies isolated from HIV-infected patients neutralize HIV-1 and have distinct autoreactivity profiles.

Danielle C Alcéna, James J Kobie, Denise A Kaminski, Alexander F Rosenberg, Jonelle L Mattiacio, Matthew Brewer, Stephen Dewhurst, Carrie Dykes, Xia Jin, Michael C Keefer and 1 more

Open access · goldAbstract readClinical Trial
In one paragraph

Trial report in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
2.1field-weighted citation impact, top 14% 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

7 citing papers in PubMed, 12 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

11 authors at 2 institutions in 1 country.

Danielle C AlcénaDepartment of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York, United States of America ; Division of Allergy, Immunology and Rheumatology, University of Rochester Medical Center, Rochester, New York, United States of America.
James J KobieDivision of Infectious Diseases, University of Rochester Medical Center, Rochester, New York, United States of America.
Denise A KaminskiDivision of Allergy, Immunology and Rheumatology, University of Rochester Medical Center, Rochester, New York, United States of America.
Alexander F RosenbergDivision of Allergy, Immunology and Rheumatology, University of Rochester Medical Center, Rochester, New York, United States of America.
Jonelle L MattiacioDepartment of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York, United States of America.
Matthew BrewerDepartment of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York, United States of America.
Stephen DewhurstDepartment of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York, United States of America.
Carrie DykesDivision of Infectious Diseases, University of Rochester Medical Center, Rochester, New York, United States of America.
Xia JinDivision of Infectious Diseases, University of Rochester Medical Center, Rochester, New York, United States of America.
Michael C KeeferDivision of Infectious Diseases, University of Rochester Medical Center, Rochester, New York, United States of America.
Ignacio SanzLowance Center for Human Immunology and Division of Rheumatology, Department of Medicine, Emory University, Atlanta, Georgia, United States of America.
University of Rochester Medical Center · USEmory University · US

Funding

Supplement - Inflammatory Triggers in B Cell AutoimmunityU19AI056363 · NIAID · DUKE UNIVERSITY · PI ST. CLAIR, EUGENE WILLIAM · 2003 to 2017
$35.3M
Virology/Immunology CoreP30AI078498 · NIAID · UNIVERSITY OF ROCHESTER · PI DEWHURST, STEPHEN · 2008 to 2018
$14.6M
A Model System for the Study of Human B-cell ToleranceR37AI049660 · NIAID · UNIVERSITY OF ROCHESTER · PI SANZ, IGNACIO E. · 2010 to 2019
$3.7M
Training in HIV Replication and PathogenesisT32AI049815 · NIAID · UNIVERSITY OF ROCHESTER · PI WEDEKIND, JOSEPH E · 2001 to 2020
$3.5M
Understanding the Generation of HIV Broadly Neutralizing AntibodiesR01AI084808 · NIAID · UNIVERSITY OF ROCHESTER · PI SANZ, IGNACIO E. · 2009 to 2013
$3.2M
Cellular Origins of HIV Broadly Neutralizing AntibodiesR21AI078459 · NIAID · UNIVERSITY OF ROCHESTER · PI SANZ, IGNACIO E. · 2008 to 2009
$535k
NIAID NIH HHS P30 AI078498NIAID NIH HHS R01 AI084808NIAID NIH HHS R01AI084808NIAID NIH HHS R21 AI078459NIAID NIH HHS R21AI078459NIAID NIH HHS R37 AI049660NIAID NIH HHS R37AI049660NIAID NIH HHS T32 AI049815NIAID NIH HHS U19 AI056363
6 · The paper itself

Abstract

Potent HIV-1 specific broadly neutralizing antibodies (BNA) are uncommon in HIV infected individuals, and have proven hard to elicit by vaccination. Several, isolated monoclonal BNA are polyreactive and also recognize self-antigens, suggesting a breach of immune tolerance in persons living with HIV (PLWH). Persons with systemic lupus erythematosus (SLE) often have elevated levels of autoreactive antibodies encoded by the VH4-34 heavy chain immunoglobulin gene whose protein product can be detected by the 9G4 rat monoclonal antibody. We have recently found that levels of these "9G4+" antibodies are also elevated in PLWH. However, the putative autoreactive nature of these antibodies and the relationship of such reactivities with HIV neutralization have not been investigated. We therefore examined the autoreactivity and HIV neutralization potential of 9G4+ antibodies from PLWH. Results show that 9G4+ antibodies from PLWH bound to recombinant HIV-1 envelope (Env) and neutralized viral infectivity in vitro, whereas 9G4+ antibodies from persons with SLE did not bind to Env and failed to neutralize viral infectivity. In addition, while 9G4+ antibodies from PLWH retained the canonical anti-i reactivity that mediates B cell binding, they did not display other autoreactivities common to SLE 9G4+ antibodies, such as binding to cardiolipin and DNA and had much lower reactivity with apoptotic cells. Taken together, these data indicate that the autoreactivity of 9G4+ antibodies from PLWH is distinct from that of SLE patients, and therefore, their expansion is not due to a general breakdown of B cell tolerance but is instead determined in a more disease-specific manner by self-antigens that become immunogenic in the context of, and possibly due to HIV infection. Further studies of 9G4+ B cells may shed light on the regulation of B cell tolerance and interface between the generation of specific autoreactivities and the induction of antiviral immunity in persons living with HIV.

Indexed as

Immune ToleranceAdultAgedAnimalsAntibodies, MonoclonalAntibodies, NeutralizingB-LymphocytesHIV AntibodiesHIV InfectionsHumansJurkat CellsLupus Erythematosus, SystemicMaleMiddle AgedRatsAntibodies, MonoclonalAntibodies, NeutralizingHIV Antibodies

Identifiers

PMID24386452
PMCPMC3873436
OpenAlexW2009684870

What OpenQuestion holds

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LicenceCC BY
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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.