Linked Life Data

15024183

Source:http://linkedlifedata.com/resource/pubmed/id/15024183

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2004-3-16
pubmed:abstractText
Intraarticular gene transfer with adeno-associated virus (AAV) vectors may allow efficient therapeutic transgene expression within the joint. In an effort to understand potential obstacles (particularly immunity against AAV vectors) to intraarticular gene therapy better, our objective was to determine whether synovial fluid (SF) influenced AAV-mediated gene transfer to chondrocytes. SF and sera from 21 patients with joint diseases were collected. Neutralizing activity against AAV/interleukin-4 (IL-4) was determined by assessing the ability of SF or serum to inhibit AAV/IL-4 transduction to the C20A4 chondrocytes. IgGs were purified from SF by salt-dependent chromatography. Anti-AAV IgG levels were determined by ELISA in the SF. SF and sera from all the patients inhibited AAV-mediated gene transfer to chondrocytes. Six SF out of 21 exerted a stronger inhibition. Serum from healthy patients were also inhibitory. Purified IgGs from SF exhibited inhibition patterns similar to those seen with whole SF. Anti-AAV IgG were found in SF from 13 patients out of 18. Moreover, in the SF, anti-AAV IgG level was correlated with the neutralizing activity (p < 0.001, r = 0.716). A correlation was observed between levels of inhibition by the SF and serum (P < 0.0001, r = 0.813). Inhibition of AAV/IL-4 infection of C20A4 cells by SF and sera was abolished by increasing the number of AAV/IL-4 particles. SF from patients with joint disease consistently inhibited AAV infection of chondrocytes in vitro. This effect was ascribable to IgG, most probably directed against AAV. In the future, these data may be useful for tailoring intraarticular AAV-mediated gene therapy to individual patients.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0271-9142
pubmed:author
pubmed:issnType
Print
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
162-9
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Immune response against gene therapy vectors: influence of synovial fluid on adeno-associated virus mediated gene transfer to chondrocytes.
pubmed:affiliation
UPRES EA-3408, Léonard de Vinci Medical School and Department of Rheumatology, Avicenne Teaching Hospital, Bobigny, AP-HP, University of Paris 13, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't