Major role of local immune responses in antibody formation to factor IX in AAV gene transfer View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2005-10

AUTHORS

L Wang, O Cao, B Swalm, E Dobrzynski, F Mingozzi, R W Herzog

ABSTRACT

The risk of an immune response to the coagulation factor IX (F.IX) transgene product is a concern in gene therapy for the X-linked bleeding disorder hemophilia B. In order to investigate the mechanism of F.IX-specific lymphocyte activation in the context of adeno-associated viral (AAV) gene transfer to skeletal muscle, we injected AAV-2 vector expressing human F.IX (hF.IX) into outbred immune-competent mice. Systemic hF.IX levels were transiently detected in the circulation, but diminished concomitant with activation of CD4+ T and B cells. ELISPOT assays documented robust responses to hF.IX in the draining lymph nodes of injected muscle by day 14. Formation of inhibitory antibodies to hF.IX was observed over a wide range of vector doses, with increased doses causing stronger immune responses. A prolonged inflammatory reaction in muscle started at 1.5-2 months, but ultimately failed to eliminate transgene expression. By 1.5 months, hF.IX antigen re-emerged in circulation in approximately 70% of animals injected with high vector dose. Hepatic gene transfer elicited only infrequent and weaker immune responses, with higher vector doses causing a reduction in T-cell responses to hF.IX. In summary, the data document substantial influence of target tissue, local antigen presentation, and antigen levels on lymphocyte responses to F.IX. More... »

PAGES

1453

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.gt.3302539

DOI

http://dx.doi.org/10.1038/sj.gt.3302539

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1042385089

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/15889137


Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
Incoming Citations Browse incoming citations for this publication using opencitations.net

JSON-LD is the canonical representation for SciGraph data.

TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

[
  {
    "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
    "about": [
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1107", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Immunology", 
        "type": "DefinedTerm"
      }, 
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/11", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Medical and Health Sciences", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Adenoviruses, Human", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Animals", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Antibodies, Blocking", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Antibody Formation", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "B-Lymphocytes", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Dependovirus", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Factor IX", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Genetic Therapy", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Genetic Vectors", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Hemophilia B", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Humans", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Injections, Intramuscular", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Interferon-gamma", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Interleukin-4", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Lymphocyte Activation", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Male", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Mice", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Mice, Inbred Strains", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Muscle, Skeletal", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "T-Lymphocytes, Helper-Inducer", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Transduction, Genetic", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Transgenes", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "Children's Hospital of Philadelphia", 
          "id": "https://www.grid.ac/institutes/grid.239552.a", 
          "name": [
            "Department of Pediatrics, University of Pennsylvania Medical Center, Philadelphia, PA, USA", 
            "The Children's Hospital of Philadelphia, Philadelphia, PA, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Wang", 
        "givenName": "L", 
        "id": "sg:person.01207565350.33", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01207565350.33"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Children's Hospital of Philadelphia", 
          "id": "https://www.grid.ac/institutes/grid.239552.a", 
          "name": [
            "Department of Pediatrics, University of Pennsylvania Medical Center, Philadelphia, PA, USA", 
            "The Children's Hospital of Philadelphia, Philadelphia, PA, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Cao", 
        "givenName": "O", 
        "id": "sg:person.01141452150.87", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01141452150.87"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Children's Hospital of Philadelphia", 
          "id": "https://www.grid.ac/institutes/grid.239552.a", 
          "name": [
            "Department of Pediatrics, University of Pennsylvania Medical Center, Philadelphia, PA, USA", 
            "The Children's Hospital of Philadelphia, Philadelphia, PA, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Swalm", 
        "givenName": "B", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Children's Hospital of Philadelphia", 
          "id": "https://www.grid.ac/institutes/grid.239552.a", 
          "name": [
            "Department of Pediatrics, University of Pennsylvania Medical Center, Philadelphia, PA, USA", 
            "The Children's Hospital of Philadelphia, Philadelphia, PA, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Dobrzynski", 
        "givenName": "E", 
        "id": "sg:person.01161766704.52", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01161766704.52"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Children's Hospital of Philadelphia", 
          "id": "https://www.grid.ac/institutes/grid.239552.a", 
          "name": [
            "Department of Pediatrics, University of Pennsylvania Medical Center, Philadelphia, PA, USA", 
            "The Children's Hospital of Philadelphia, Philadelphia, PA, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Mingozzi", 
        "givenName": "F", 
        "id": "sg:person.01145473703.03", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01145473703.03"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Children's Hospital of Philadelphia", 
          "id": "https://www.grid.ac/institutes/grid.239552.a", 
          "name": [
            "Department of Pediatrics, University of Pennsylvania Medical Center, Philadelphia, PA, USA", 
            "The Children's Hospital of Philadelphia, Philadelphia, PA, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Herzog", 
        "givenName": "R W", 
        "id": "sg:person.0764614376.16", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0764614376.16"
        ], 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "https://doi.org/10.1073/pnas.96.7.3906", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1000199188"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1006/mthe.2000.0032", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1000875436"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1182/blood-2002-10-3296", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1003619350"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/4743", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1005137439", 
          "https://doi.org/10.1038/4743"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/4743", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1005137439", 
          "https://doi.org/10.1038/4743"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.ymthe.2004.05.054", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1006009428"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1182/blood-2003-05-1446", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1006032100"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1182/blood-2004-03-0847", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1006869449"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1182/blood-2004-08-2990", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1008100532"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1182/blood.v97.5.1258", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1009816932"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/jvi.78.6.3110-3122.2004", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1013436925"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1073/pnas.83.23.9169", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1014622564"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1182/blood-2004-03-0848", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1017483087"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/jvi.75.1.269-277.2001", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1018912222"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1182/blood.v99.8.2670", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1019564621"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1006/mthe.2001.0333", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1020301228"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1146/annurev.immunol.18.1.767", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1023617086"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1006/mthe.2001.0449", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1024916662"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1182/blood-2004-03-1028", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1027405277"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/jvi.76.9.4580-4590.2002", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1030362387"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1006/mthe.2001.0441", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1031352725"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1385/1-59259-650-9:179", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1036002183", 
          "https://doi.org/10.1385/1-59259-650-9:179"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ng0797-270", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1038688300", 
          "https://doi.org/10.1038/ng0797-270"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1006/mthe.2001.0442", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1042063468"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/4751", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1043560823", 
          "https://doi.org/10.1038/4751"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/4751", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1043560823", 
          "https://doi.org/10.1038/4751"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1073/pnas.94.11.5804", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1046830591"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.gt.3302233", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1051233580", 
          "https://doi.org/10.1038/sj.gt.3302233"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.gt.3302233", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1051233580", 
          "https://doi.org/10.1038/sj.gt.3302233"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1055/s-2003-37945", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1057420549"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1055/s-2004-825635", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1057433576"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1089/104303402760128513", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1059202474"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1089/1043034041648453", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1059202690"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1172/jci16887", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1063416239"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.4049/jimmunol.166.10.6099", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1074810696"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1055/s-0037-1613094", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1075061808"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1076797264", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1083249128", 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2005-10", 
    "datePublishedReg": "2005-10-01", 
    "description": "The risk of an immune response to the coagulation factor IX (F.IX) transgene product is a concern in gene therapy for the X-linked bleeding disorder hemophilia B. In order to investigate the mechanism of F.IX-specific lymphocyte activation in the context of adeno-associated viral (AAV) gene transfer to skeletal muscle, we injected AAV-2 vector expressing human F.IX (hF.IX) into outbred immune-competent mice. Systemic hF.IX levels were transiently detected in the circulation, but diminished concomitant with activation of CD4+ T and B cells. ELISPOT assays documented robust responses to hF.IX in the draining lymph nodes of injected muscle by day 14. Formation of inhibitory antibodies to hF.IX was observed over a wide range of vector doses, with increased doses causing stronger immune responses. A prolonged inflammatory reaction in muscle started at 1.5-2 months, but ultimately failed to eliminate transgene expression. By 1.5 months, hF.IX antigen re-emerged in circulation in approximately 70% of animals injected with high vector dose. Hepatic gene transfer elicited only infrequent and weaker immune responses, with higher vector doses causing a reduction in T-cell responses to hF.IX. In summary, the data document substantial influence of target tissue, local antigen presentation, and antigen levels on lymphocyte responses to F.IX.", 
    "genre": "research_article", 
    "id": "sg:pub.10.1038/sj.gt.3302539", 
    "inLanguage": [
      "en"
    ], 
    "isAccessibleForFree": true, 
    "isFundedItemOf": [
      {
        "id": "sg:grant.2684706", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.2691684", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.2455752", 
        "type": "MonetaryGrant"
      }
    ], 
    "isPartOf": [
      {
        "id": "sg:journal.1105638", 
        "issn": [
          "0969-7128", 
          "1476-5462"
        ], 
        "name": "Gene Therapy", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "19", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "12"
      }
    ], 
    "name": "Major role of local immune responses in antibody formation to factor IX in AAV gene transfer", 
    "pagination": "1453", 
    "productId": [
      {
        "name": "readcube_id", 
        "type": "PropertyValue", 
        "value": [
          "c9e639c68c9000a319b1932ae7f9eae024d5e47d988375129de857a0dddf02e4"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "15889137"
        ]
      }, 
      {
        "name": "nlm_unique_id", 
        "type": "PropertyValue", 
        "value": [
          "9421525"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1038/sj.gt.3302539"
        ]
      }, 
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1042385089"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1038/sj.gt.3302539", 
      "https://app.dimensions.ai/details/publication/pub.1042385089"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2019-04-11T12:05", 
    "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
    "sdPublisher": {
      "name": "Springer Nature - SN SciGraph project", 
      "type": "Organization"
    }, 
    "sdSource": "s3://com-uberresearch-data-dimensions-target-20181106-alternative/cleanup/v134/2549eaecd7973599484d7c17b260dba0a4ecb94b/merge/v9/a6c9fde33151104705d4d7ff012ea9563521a3ce/jats-lookup/v90/0000000360_0000000360/records_118324_00000001.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "https://www.nature.com/articles/3302539"
  }
]
 

Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/sj.gt.3302539'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/sj.gt.3302539'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/sj.gt.3302539'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/sj.gt.3302539'


 

This table displays all metadata directly associated to this object as RDF triples.

306 TRIPLES      21 PREDICATES      86 URIs      43 LITERALS      31 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1038/sj.gt.3302539 schema:about N062c574aa7214e55bd08fab38ab743e7
2 N06b85635eb864b0dbd746e5217d356b3
3 N17febd095c104dc4ae76370c22cefc6f
4 N1dcc5dfa6c6c4c0c81d60cf55bd4935a
5 N32e2d4c133314ca59a50ee0a2f9112d0
6 N57b31ca01eed4e3aafa31eecd48a60e8
7 N62ce4b00371d4bf1a6dd7f40f8fb0448
8 N6e6940ee1ed34a5494b2d8963b1ed66f
9 N6fd024a797a34a0a8dc1846354337e0f
10 N77ec6a5e31bf478b8d10e15c04cc3387
11 N88194627e2964d5784218043697693e8
12 N8d4572478aa14804b08552acd6afe414
13 Na90843ee4cf84c85a593a027c3617da8
14 Naf87b732e6204c108fb9ffee3d26cbf1
15 Nc2fdd55f890a44529cfd33e11c4468bb
16 Nd4ad8eb11dc64e27b989e137c139f642
17 Nda00c52cd7ac44dfb21197602dd4f1e6
18 Ndd7dd902a06045e4ba5637157fc3af93
19 Nf0d562973e414183957a3e57ab77fdc2
20 Nf1819d7e9bb2434a87eb185815a16c01
21 Nf7d21648e7a44768a073a561e608e02e
22 Nfedb433f275c46eca7b20036e8bfc3a9
23 anzsrc-for:11
24 anzsrc-for:1107
25 schema:author Nad33df8b5efd4ab9b58e60befb65c01f
26 schema:citation sg:pub.10.1038/4743
27 sg:pub.10.1038/4751
28 sg:pub.10.1038/ng0797-270
29 sg:pub.10.1038/sj.gt.3302233
30 sg:pub.10.1385/1-59259-650-9:179
31 https://app.dimensions.ai/details/publication/pub.1076797264
32 https://app.dimensions.ai/details/publication/pub.1083249128
33 https://doi.org/10.1006/mthe.2000.0032
34 https://doi.org/10.1006/mthe.2001.0333
35 https://doi.org/10.1006/mthe.2001.0441
36 https://doi.org/10.1006/mthe.2001.0442
37 https://doi.org/10.1006/mthe.2001.0449
38 https://doi.org/10.1016/j.ymthe.2004.05.054
39 https://doi.org/10.1055/s-0037-1613094
40 https://doi.org/10.1055/s-2003-37945
41 https://doi.org/10.1055/s-2004-825635
42 https://doi.org/10.1073/pnas.83.23.9169
43 https://doi.org/10.1073/pnas.94.11.5804
44 https://doi.org/10.1073/pnas.96.7.3906
45 https://doi.org/10.1089/104303402760128513
46 https://doi.org/10.1089/1043034041648453
47 https://doi.org/10.1128/jvi.75.1.269-277.2001
48 https://doi.org/10.1128/jvi.76.9.4580-4590.2002
49 https://doi.org/10.1128/jvi.78.6.3110-3122.2004
50 https://doi.org/10.1146/annurev.immunol.18.1.767
51 https://doi.org/10.1172/jci16887
52 https://doi.org/10.1182/blood-2002-10-3296
53 https://doi.org/10.1182/blood-2003-05-1446
54 https://doi.org/10.1182/blood-2004-03-0847
55 https://doi.org/10.1182/blood-2004-03-0848
56 https://doi.org/10.1182/blood-2004-03-1028
57 https://doi.org/10.1182/blood-2004-08-2990
58 https://doi.org/10.1182/blood.v97.5.1258
59 https://doi.org/10.1182/blood.v99.8.2670
60 https://doi.org/10.4049/jimmunol.166.10.6099
61 schema:datePublished 2005-10
62 schema:datePublishedReg 2005-10-01
63 schema:description The risk of an immune response to the coagulation factor IX (F.IX) transgene product is a concern in gene therapy for the X-linked bleeding disorder hemophilia B. In order to investigate the mechanism of F.IX-specific lymphocyte activation in the context of adeno-associated viral (AAV) gene transfer to skeletal muscle, we injected AAV-2 vector expressing human F.IX (hF.IX) into outbred immune-competent mice. Systemic hF.IX levels were transiently detected in the circulation, but diminished concomitant with activation of CD4+ T and B cells. ELISPOT assays documented robust responses to hF.IX in the draining lymph nodes of injected muscle by day 14. Formation of inhibitory antibodies to hF.IX was observed over a wide range of vector doses, with increased doses causing stronger immune responses. A prolonged inflammatory reaction in muscle started at 1.5-2 months, but ultimately failed to eliminate transgene expression. By 1.5 months, hF.IX antigen re-emerged in circulation in approximately 70% of animals injected with high vector dose. Hepatic gene transfer elicited only infrequent and weaker immune responses, with higher vector doses causing a reduction in T-cell responses to hF.IX. In summary, the data document substantial influence of target tissue, local antigen presentation, and antigen levels on lymphocyte responses to F.IX.
64 schema:genre research_article
65 schema:inLanguage en
66 schema:isAccessibleForFree true
67 schema:isPartOf N15da215a90b04399b5c598b29e8313c4
68 Nbb440e4bbbc744faad45954e21dab59e
69 sg:journal.1105638
70 schema:name Major role of local immune responses in antibody formation to factor IX in AAV gene transfer
71 schema:pagination 1453
72 schema:productId N5a34db4a4432448396f4dd0bdf93788a
73 N71215ab9e31e4a7a96f86ae0557a6326
74 N888e1d5ff962443dadcf5ff99d4b3f14
75 Nbb71f5d01bc44e1b811d9f513833ef2e
76 Nf2eb3b99d754476996d81e1cadcf4a2c
77 schema:sameAs https://app.dimensions.ai/details/publication/pub.1042385089
78 https://doi.org/10.1038/sj.gt.3302539
79 schema:sdDatePublished 2019-04-11T12:05
80 schema:sdLicense https://scigraph.springernature.com/explorer/license/
81 schema:sdPublisher N238738b799ff44519381b796d8cfad5f
82 schema:url https://www.nature.com/articles/3302539
83 sgo:license sg:explorer/license/
84 sgo:sdDataset articles
85 rdf:type schema:ScholarlyArticle
86 N062c574aa7214e55bd08fab38ab743e7 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
87 schema:name Adenoviruses, Human
88 rdf:type schema:DefinedTerm
89 N06b85635eb864b0dbd746e5217d356b3 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
90 schema:name Lymphocyte Activation
91 rdf:type schema:DefinedTerm
92 N0c94876dc0ef4676ac651f33d1da8826 rdf:first sg:person.0764614376.16
93 rdf:rest rdf:nil
94 N15da215a90b04399b5c598b29e8313c4 schema:volumeNumber 12
95 rdf:type schema:PublicationVolume
96 N17febd095c104dc4ae76370c22cefc6f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
97 schema:name Mice
98 rdf:type schema:DefinedTerm
99 N1dcc5dfa6c6c4c0c81d60cf55bd4935a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
100 schema:name T-Lymphocytes, Helper-Inducer
101 rdf:type schema:DefinedTerm
102 N238738b799ff44519381b796d8cfad5f schema:name Springer Nature - SN SciGraph project
103 rdf:type schema:Organization
104 N2c76b5bcb226497992f232fc2e224de8 rdf:first Na26fa156ca99407bbc9d2c7149190f0c
105 rdf:rest Nf743f6846b3945aaae65f16df6a5aed5
106 N32e2d4c133314ca59a50ee0a2f9112d0 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
107 schema:name Hemophilia B
108 rdf:type schema:DefinedTerm
109 N331e13ef534f4579bb9a93d75843e172 rdf:first sg:person.01141452150.87
110 rdf:rest N2c76b5bcb226497992f232fc2e224de8
111 N41b5443cd07f4459b410a5d79e7b6a38 rdf:first sg:person.01145473703.03
112 rdf:rest N0c94876dc0ef4676ac651f33d1da8826
113 N57b31ca01eed4e3aafa31eecd48a60e8 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
114 schema:name Factor IX
115 rdf:type schema:DefinedTerm
116 N5a34db4a4432448396f4dd0bdf93788a schema:name doi
117 schema:value 10.1038/sj.gt.3302539
118 rdf:type schema:PropertyValue
119 N62ce4b00371d4bf1a6dd7f40f8fb0448 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
120 schema:name Genetic Vectors
121 rdf:type schema:DefinedTerm
122 N6e6940ee1ed34a5494b2d8963b1ed66f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
123 schema:name Animals
124 rdf:type schema:DefinedTerm
125 N6fd024a797a34a0a8dc1846354337e0f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
126 schema:name Male
127 rdf:type schema:DefinedTerm
128 N71215ab9e31e4a7a96f86ae0557a6326 schema:name nlm_unique_id
129 schema:value 9421525
130 rdf:type schema:PropertyValue
131 N77ec6a5e31bf478b8d10e15c04cc3387 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
132 schema:name Mice, Inbred Strains
133 rdf:type schema:DefinedTerm
134 N88194627e2964d5784218043697693e8 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
135 schema:name Transduction, Genetic
136 rdf:type schema:DefinedTerm
137 N888e1d5ff962443dadcf5ff99d4b3f14 schema:name dimensions_id
138 schema:value pub.1042385089
139 rdf:type schema:PropertyValue
140 N8d4572478aa14804b08552acd6afe414 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
141 schema:name Muscle, Skeletal
142 rdf:type schema:DefinedTerm
143 Na26fa156ca99407bbc9d2c7149190f0c schema:affiliation https://www.grid.ac/institutes/grid.239552.a
144 schema:familyName Swalm
145 schema:givenName B
146 rdf:type schema:Person
147 Na90843ee4cf84c85a593a027c3617da8 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
148 schema:name Humans
149 rdf:type schema:DefinedTerm
150 Nad33df8b5efd4ab9b58e60befb65c01f rdf:first sg:person.01207565350.33
151 rdf:rest N331e13ef534f4579bb9a93d75843e172
152 Naf87b732e6204c108fb9ffee3d26cbf1 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
153 schema:name Interferon-gamma
154 rdf:type schema:DefinedTerm
155 Nbb440e4bbbc744faad45954e21dab59e schema:issueNumber 19
156 rdf:type schema:PublicationIssue
157 Nbb71f5d01bc44e1b811d9f513833ef2e schema:name readcube_id
158 schema:value c9e639c68c9000a319b1932ae7f9eae024d5e47d988375129de857a0dddf02e4
159 rdf:type schema:PropertyValue
160 Nc2fdd55f890a44529cfd33e11c4468bb schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
161 schema:name B-Lymphocytes
162 rdf:type schema:DefinedTerm
163 Nd4ad8eb11dc64e27b989e137c139f642 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
164 schema:name Dependovirus
165 rdf:type schema:DefinedTerm
166 Nda00c52cd7ac44dfb21197602dd4f1e6 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
167 schema:name Genetic Therapy
168 rdf:type schema:DefinedTerm
169 Ndd7dd902a06045e4ba5637157fc3af93 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
170 schema:name Antibody Formation
171 rdf:type schema:DefinedTerm
172 Nf0d562973e414183957a3e57ab77fdc2 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
173 schema:name Injections, Intramuscular
174 rdf:type schema:DefinedTerm
175 Nf1819d7e9bb2434a87eb185815a16c01 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
176 schema:name Interleukin-4
177 rdf:type schema:DefinedTerm
178 Nf2eb3b99d754476996d81e1cadcf4a2c schema:name pubmed_id
179 schema:value 15889137
180 rdf:type schema:PropertyValue
181 Nf743f6846b3945aaae65f16df6a5aed5 rdf:first sg:person.01161766704.52
182 rdf:rest N41b5443cd07f4459b410a5d79e7b6a38
183 Nf7d21648e7a44768a073a561e608e02e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
184 schema:name Antibodies, Blocking
185 rdf:type schema:DefinedTerm
186 Nfedb433f275c46eca7b20036e8bfc3a9 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
187 schema:name Transgenes
188 rdf:type schema:DefinedTerm
189 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
190 schema:name Medical and Health Sciences
191 rdf:type schema:DefinedTerm
192 anzsrc-for:1107 schema:inDefinedTermSet anzsrc-for:
193 schema:name Immunology
194 rdf:type schema:DefinedTerm
195 sg:grant.2455752 http://pending.schema.org/fundedItem sg:pub.10.1038/sj.gt.3302539
196 rdf:type schema:MonetaryGrant
197 sg:grant.2684706 http://pending.schema.org/fundedItem sg:pub.10.1038/sj.gt.3302539
198 rdf:type schema:MonetaryGrant
199 sg:grant.2691684 http://pending.schema.org/fundedItem sg:pub.10.1038/sj.gt.3302539
200 rdf:type schema:MonetaryGrant
201 sg:journal.1105638 schema:issn 0969-7128
202 1476-5462
203 schema:name Gene Therapy
204 rdf:type schema:Periodical
205 sg:person.01141452150.87 schema:affiliation https://www.grid.ac/institutes/grid.239552.a
206 schema:familyName Cao
207 schema:givenName O
208 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01141452150.87
209 rdf:type schema:Person
210 sg:person.01145473703.03 schema:affiliation https://www.grid.ac/institutes/grid.239552.a
211 schema:familyName Mingozzi
212 schema:givenName F
213 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01145473703.03
214 rdf:type schema:Person
215 sg:person.01161766704.52 schema:affiliation https://www.grid.ac/institutes/grid.239552.a
216 schema:familyName Dobrzynski
217 schema:givenName E
218 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01161766704.52
219 rdf:type schema:Person
220 sg:person.01207565350.33 schema:affiliation https://www.grid.ac/institutes/grid.239552.a
221 schema:familyName Wang
222 schema:givenName L
223 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01207565350.33
224 rdf:type schema:Person
225 sg:person.0764614376.16 schema:affiliation https://www.grid.ac/institutes/grid.239552.a
226 schema:familyName Herzog
227 schema:givenName R W
228 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0764614376.16
229 rdf:type schema:Person
230 sg:pub.10.1038/4743 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005137439
231 https://doi.org/10.1038/4743
232 rdf:type schema:CreativeWork
233 sg:pub.10.1038/4751 schema:sameAs https://app.dimensions.ai/details/publication/pub.1043560823
234 https://doi.org/10.1038/4751
235 rdf:type schema:CreativeWork
236 sg:pub.10.1038/ng0797-270 schema:sameAs https://app.dimensions.ai/details/publication/pub.1038688300
237 https://doi.org/10.1038/ng0797-270
238 rdf:type schema:CreativeWork
239 sg:pub.10.1038/sj.gt.3302233 schema:sameAs https://app.dimensions.ai/details/publication/pub.1051233580
240 https://doi.org/10.1038/sj.gt.3302233
241 rdf:type schema:CreativeWork
242 sg:pub.10.1385/1-59259-650-9:179 schema:sameAs https://app.dimensions.ai/details/publication/pub.1036002183
243 https://doi.org/10.1385/1-59259-650-9:179
244 rdf:type schema:CreativeWork
245 https://app.dimensions.ai/details/publication/pub.1076797264 schema:CreativeWork
246 https://app.dimensions.ai/details/publication/pub.1083249128 schema:CreativeWork
247 https://doi.org/10.1006/mthe.2000.0032 schema:sameAs https://app.dimensions.ai/details/publication/pub.1000875436
248 rdf:type schema:CreativeWork
249 https://doi.org/10.1006/mthe.2001.0333 schema:sameAs https://app.dimensions.ai/details/publication/pub.1020301228
250 rdf:type schema:CreativeWork
251 https://doi.org/10.1006/mthe.2001.0441 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031352725
252 rdf:type schema:CreativeWork
253 https://doi.org/10.1006/mthe.2001.0442 schema:sameAs https://app.dimensions.ai/details/publication/pub.1042063468
254 rdf:type schema:CreativeWork
255 https://doi.org/10.1006/mthe.2001.0449 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024916662
256 rdf:type schema:CreativeWork
257 https://doi.org/10.1016/j.ymthe.2004.05.054 schema:sameAs https://app.dimensions.ai/details/publication/pub.1006009428
258 rdf:type schema:CreativeWork
259 https://doi.org/10.1055/s-0037-1613094 schema:sameAs https://app.dimensions.ai/details/publication/pub.1075061808
260 rdf:type schema:CreativeWork
261 https://doi.org/10.1055/s-2003-37945 schema:sameAs https://app.dimensions.ai/details/publication/pub.1057420549
262 rdf:type schema:CreativeWork
263 https://doi.org/10.1055/s-2004-825635 schema:sameAs https://app.dimensions.ai/details/publication/pub.1057433576
264 rdf:type schema:CreativeWork
265 https://doi.org/10.1073/pnas.83.23.9169 schema:sameAs https://app.dimensions.ai/details/publication/pub.1014622564
266 rdf:type schema:CreativeWork
267 https://doi.org/10.1073/pnas.94.11.5804 schema:sameAs https://app.dimensions.ai/details/publication/pub.1046830591
268 rdf:type schema:CreativeWork
269 https://doi.org/10.1073/pnas.96.7.3906 schema:sameAs https://app.dimensions.ai/details/publication/pub.1000199188
270 rdf:type schema:CreativeWork
271 https://doi.org/10.1089/104303402760128513 schema:sameAs https://app.dimensions.ai/details/publication/pub.1059202474
272 rdf:type schema:CreativeWork
273 https://doi.org/10.1089/1043034041648453 schema:sameAs https://app.dimensions.ai/details/publication/pub.1059202690
274 rdf:type schema:CreativeWork
275 https://doi.org/10.1128/jvi.75.1.269-277.2001 schema:sameAs https://app.dimensions.ai/details/publication/pub.1018912222
276 rdf:type schema:CreativeWork
277 https://doi.org/10.1128/jvi.76.9.4580-4590.2002 schema:sameAs https://app.dimensions.ai/details/publication/pub.1030362387
278 rdf:type schema:CreativeWork
279 https://doi.org/10.1128/jvi.78.6.3110-3122.2004 schema:sameAs https://app.dimensions.ai/details/publication/pub.1013436925
280 rdf:type schema:CreativeWork
281 https://doi.org/10.1146/annurev.immunol.18.1.767 schema:sameAs https://app.dimensions.ai/details/publication/pub.1023617086
282 rdf:type schema:CreativeWork
283 https://doi.org/10.1172/jci16887 schema:sameAs https://app.dimensions.ai/details/publication/pub.1063416239
284 rdf:type schema:CreativeWork
285 https://doi.org/10.1182/blood-2002-10-3296 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003619350
286 rdf:type schema:CreativeWork
287 https://doi.org/10.1182/blood-2003-05-1446 schema:sameAs https://app.dimensions.ai/details/publication/pub.1006032100
288 rdf:type schema:CreativeWork
289 https://doi.org/10.1182/blood-2004-03-0847 schema:sameAs https://app.dimensions.ai/details/publication/pub.1006869449
290 rdf:type schema:CreativeWork
291 https://doi.org/10.1182/blood-2004-03-0848 schema:sameAs https://app.dimensions.ai/details/publication/pub.1017483087
292 rdf:type schema:CreativeWork
293 https://doi.org/10.1182/blood-2004-03-1028 schema:sameAs https://app.dimensions.ai/details/publication/pub.1027405277
294 rdf:type schema:CreativeWork
295 https://doi.org/10.1182/blood-2004-08-2990 schema:sameAs https://app.dimensions.ai/details/publication/pub.1008100532
296 rdf:type schema:CreativeWork
297 https://doi.org/10.1182/blood.v97.5.1258 schema:sameAs https://app.dimensions.ai/details/publication/pub.1009816932
298 rdf:type schema:CreativeWork
299 https://doi.org/10.1182/blood.v99.8.2670 schema:sameAs https://app.dimensions.ai/details/publication/pub.1019564621
300 rdf:type schema:CreativeWork
301 https://doi.org/10.4049/jimmunol.166.10.6099 schema:sameAs https://app.dimensions.ai/details/publication/pub.1074810696
302 rdf:type schema:CreativeWork
303 https://www.grid.ac/institutes/grid.239552.a schema:alternateName Children's Hospital of Philadelphia
304 schema:name Department of Pediatrics, University of Pennsylvania Medical Center, Philadelphia, PA, USA
305 The Children's Hospital of Philadelphia, Philadelphia, PA, USA
306 rdf:type schema:Organization
 




Preview window. Press ESC to close (or click here)


...