Evidence map›Paper›PMID 29925682›Full record

ArticleJCI insight2018

Enhancing IgG distribution to lung mucosal tissue improves protective effect of anti-Pseudomonas aeruginosa antibodies.

M Jack Borrok, Antonio DiGiandomenico, Nurten Beyaz, Gabriela M Marchetti, Arnita S Barnes, Kristen J Lekstrom, Sandrina S Phipps, Michael P McCarthy, Herren Wu, William F Dall'Acqua and 2 more

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 1 pooled it
1.3field-weighted citation impact, top 19% 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

18 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.

  1. Pooled it
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  12. Intravenous anti-Innate immunity · 2022
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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

12 authors at 1 institution in 1 country.

M Jack BorrokAntibody Discovery and Protein Engineering.
Antonio DiGiandomenicoMicrobial Sciences, and.
Nurten BeyazAntibody Discovery and Protein Engineering.
Gabriela M MarchettiAntibody Discovery and Protein Engineering.
Arnita S BarnesAntibody Discovery and Protein Engineering.
Kristen J LekstromAntibody Discovery and Protein Engineering.
Sandrina S PhippsAntibody Discovery and Protein Engineering.
Michael P McCarthyMicrobial Sciences, and.
Herren WuAntibody Discovery and Protein Engineering.
William F Dall'AcquaAntibody Discovery and Protein Engineering.
Ping TsuiAntibody Discovery and Protein Engineering.
Ruchi GuptaCardiovascular, Renal, and Metabolic Disease, MedImmune, Gaithersburg, Maryland, USA.
Altimmune (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

IgG antibodies are abundantly present in the vasculature but to a much lesser extent in mucosal tissues. This contrasts with antibodies of the IgA and IgM isotype that are present at high concentration in mucosal secretions due to active delivery by the polymeric Ig receptor (pIgR). IgG is the preferred isotype for therapeutic mAb development due to its long serum half-life and robust Fc-mediated effector function, and it is utilized to treat a diverse array of diseases with antigen targets located in the vasculature, serosa, and mucosa. As therapeutic IgG antibodies targeting the luminal side of mucosal tissue lack an active transport delivery mechanism, we sought to generate IgG antibodies that could be transported via pIgR, similarly to dimeric IgA and pentameric IgM. We show that an anti-Pseudomonas aeruginosa IgG fused with pIgR-binding peptides gained the ability to transcytose and be secreted via pIgR. Consistent with these results, pIgR-binding IgG antibodies exhibit enhanced localization to the bronchoalveolar space when compared with the parental IgG antibody. Furthermore, pIgR-binding mAbs maintained Fc-mediated functional activity and promoted enhanced survival compared with the parental mAb in a P. aeruginosa acute pneumonia model. Our results suggest that increasing IgG accumulation at mucosal surfaces by pIgR-mediated active transport can improve the efficacy of therapeutic mAbs that act at these sites.

Indexed as

AnimalsBiological TransportCHO CellsCricetulusDogsImmunoglobulin AImmunoglobulin GImmunoglobulin MMadin Darby Canine Kidney CellsMice, Inbred BALB CMucous MembranePseudomonas aeruginosaPseudomonas InfectionsReceptors, Polymeric ImmunoglobulinSecretory ComponentTranscytosisImmunoglobulin AImmunoglobulin GImmunoglobulin MReceptors, Polymeric ImmunoglobulinSecretory ComponentBacterial infectionsImmunoglobulinsInfectious diseasePharmacologyTherapeutics

Identifiers

PMID29925682
PMCPMC6124411
OpenAlexW2808892459

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.