Evidence map›Paper›PMID 23649621›Full record

ArticleThe Journal of biological chemistry2013

Exposure to factor VIII protein in the presence of phosphatidylserine induces hypo-responsiveness toward factor VIII challenge in hemophilia A mice.

Puneet Gaitonde, Radha Ramakrishnan, Jamie Chin, Raymond J Kelleher, Richard B Bankert, Sathy V Balu-Iyer

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
1.6field-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

27 citing papers in PubMed, 33 citations in OpenAlex.

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  15. Immunogenicity of Protein Pharmaceuticals.Journal of pharmaceutical sciences · 2019
    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

6 authors at 1 institution in 1 country.

Puneet GaitondeDepartment of Pharmaceutical Sciences, University at Buffalo, The State University of New York, Buffalo, New York 14214, USA.
Radha Ramakrishnan
Jamie Chin
Raymond J Kelleher
Richard B Bankert
Sathy V Balu-Iyer
University at Buffalo, State University of New York · US

Funding

HL-Development and Pharmacology of novel lipidic rAHF and biotherapeuticsR01HL070227 · NHLBI · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI BALU-IYER, SATHY VENKAT · 2002 to 2019
$5.0M
Re-activating Memory T Cells in the Microenvironment of Human TumorsR01CA131407 · NCI · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI BANKERT, RICHARD B · 2008 to 2017
$3.4M
CD4+ Memory T-Cells in Human Tumor MicroenvironmentR01CA108970 · NCI · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI BANKERT, RICHARD B · 2005 to 2014
$3.0M
NCI NIH HHS R01 CA108970NCI NIH HHS R01 CA131407NHLBI NIH HHS R01 HL070227NHLBI NIH HHS R01 HL-70227
6 · The paper itself

Abstract

Administration of recombinant factor VIII (FVIII), an important co-factor in blood clotting cascade, elicits unwanted anti-FVIII antibodies in hemophilia A (HA) patients. Previously, FVIII associated with phosphatidylserine (PS) showed significant reduction in the anti-FVIII antibody response in HA mice. The reduction in the immune response to FVIII-PS could be due either to a failure of the immune system to recognize the antigen (i.e. immunological ignorance) or to an active induction of an antigen-specific nonresponsiveness (i.e. immunological tolerance). If it were a result of tolerance, one would predict that pre-exposure to FVIII-PS would render the mice hypo-responsive to a subsequent FVIII challenge. Here, we have demonstrated that naive HA mice that were pretreated with FVIII-PS showed a significantly reduced FVIII immune response to further challenge with native FVIII and that this decreased responsiveness could be adoptively transferred to other mice. An increase in number of FoxP3-expressing CD4(+) regulatory T-cells (Treg) was observed for the FVIII-PS-immunized group as compared with animals that received FVIII alone, suggesting the involvement of Treg in PS-mediated hypo-responsiveness. The PS-mediated reduction in antibody response was reversed by the co-administration of function-blocking anti-TGF-β antibody with FVIII-PS. The decreased response to FVIII induced by FVIII-PS was determined to be antigen-specific because the immune response to another non-cross-reactive antigen (ovalbumin) was not altered. These results are consistent with the notion that FVIII-PS is tolerogenic and suggest that immunization with this tolerogenic form of the protein could be a useful treatment option to minimize immunogenicity of FVIII and other protein-based therapeutics.

Indexed as

Adjuvants, ImmunologicAdoptive TransferAnimalsAntibodies, NeutralizingFactor VIIIForkhead Transcription FactorsHemophilia AHumansImmune ToleranceMiceMice, KnockoutPhosphatidylserinesT-Lymphocytes, RegulatoryAdjuvants, ImmunologicAntibodies, NeutralizingFactor VIIIForkhead Transcription FactorsFoxp3 protein, mousePhosphatidylserinesBiotechnologyBlood Coagulation FactorsDendritic CellsFactor VIIIGFP-FoxP3Immunological ToleranceImmunosuppressionPhosphatidylserineRegulatory T-cellReverse/Inverse Vaccination

Identifiers

PMID23649621
PMCPMC3682509
OpenAlexW2002826770

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.