Evidence map›Paper›PMID 23836278›Full record

ArticleHuman vaccines & immunotherapeutics2013

Multi-therapeutic potential of autoantibodies induced by immune complexes trapped on follicular dendritic cells.

Mohey Eldin El Shikh, Maciej Kmieciak, Masoud H Manjili, Andras K Szakal, Costantino Pitzalis, John G Tew

Abstract read
In one paragraph

Article in Human vaccines & immunotherapeutics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Mohey Eldin El ShikhCentre for Experimental Medicine and Rheumatology; William Harvey Research Institute; Barts and the London School of Medicine and Dentistry; Queen Mary University of London; London, UK.
Maciej Kmieciak
Masoud H Manjili
Andras K Szakal
Costantino Pitzalis
John G Tew

Funding

ROLE OF FOLLICULAR ANTIGEN-BINDING DENDRITIC CELLSR01AI017142 · NIAID · VIRGINIA COMMONWEALTH UNIVERSITY · PI TEW, JOHN G · 1985 to 2006
$1.7M
Follicular Antigen Binding Dendritic CellsR56AI017142 · NIAID · VIRGINIA COMMONWEALTH UNIVERSITY · PI TEW, JOHN G · 2008 to 2009
$666k
NIAID NIH HHS AI-017142NIAID NIH HHS R01 AI017142NIAID NIH HHS R56 AI017142
6 · The paper itself

Abstract

Induction of autoantibodies (autoAbs) targeting disease drivers / mediators is emerging as a potential immunotherapeutic strategy. Auto-immune complex (IC)-retaining follicular dendritic cells (FDCs) critically regulate pathogenic autoAb production in autoreactive germinal centers (GCs); however, their ability to induce potentially therapeutic autoAbs has not been explored. We hypothesized that deliberate display of clinically targeted antigens (Ags) in the form of ICs on FDC membranes induces target-specific autoreactive GCs and autoAbs that may be exploited therapeutically. To test our hypothesis, three therapeutically relevant Ags: TNF-α, HER2/neu and IgE, were investigated. Our results indicated that TNF-α-, HER2/neu- and IgE-specific autoAbs associated with strong GC reactions were induced by TNF-α-, HER2/neu- and IgE-IC retention on FDCs. Moreover, the induced anti-TNF-α autoAbs neutralized mouse and human TNF-α with half maximal Inhibitory Concentration (IC₅₀) of 7.1 and 1.6 nM respectively. In addition, we demonstrated that FDC-induced Ab production could be non-specifically inhibited by the IgG-specific Endo-S that accessed the light zones of GCs and interfered with FDC-IC retention. In conclusion, the ability of FDCs to productively present autoAgs raises the potential for a novel immunotherapeutic platform targeting mediators of autoimmune disorders, allergic diseases, and Ab responsive cancers.

Indexed as

AnimalsAntibodies, NeutralizingAntigen-Antibody ComplexAutoantibodiesDendritic Cells, FollicularHumansInhibitory Concentration 50Mice, Inbred BALB CAntibodies, NeutralizingAntigen-Antibody ComplexAutoantibodiesautoantibodiesfollicular dendritic cellgerminal centreimmune complexesimmunotherapeutic

Identifiers

PMID23836278
PMCPMC3981854

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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.