Immune Response Against Gene Therapy Vectors: Influence of Synovial Fluid on Adeno-Associated Virus Mediated Gene Transfer to Chondrocytes
- 1 March 2004
- journal article
- Published by Springer Science and Business Media LLC in Journal of Clinical Immunology
- Vol. 24 (2), 162-169
- https://doi.org/10.1023/b:joci.0000019781.64421.5c
Abstract
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.This publication has 26 references indexed in Scilit:
- Recombinant Adeno-Associated Virus Vectors Efficiently and Persistently Transduce Chondrocytes in Normal and Osteoarthritic Human Articular CartilageHuman Gene Therapy, 2003
- Gene therapy for rheumatoid arthritisThe Journal of Gene Medicine, 2002
- The influence of synovial fluid on adenovirus-mediated gene transfer to the synovial tissueArthritis & Rheumatism, 2001
- Epitope Mapping of Human Anti-Adeno-Associated Virus Type 2 Neutralizing Antibodies: Implications for Gene Therapy and Virus StructureJournal of Virology, 2000
- Update on the prevalence of serum antibodies (IgG and IgM) to adeno-associated virus (AAV)Journal of Medical Virology, 1999
- Recombinant adeno-associated virus for muscle directed gene therapyNature Medicine, 1997
- Use of thiophilic adsorption in the purification of biotinylated Fab fragmentsJournal of Chromatography B: Biomedical Sciences and Applications, 1995
- Interleukin-1 beta-modulated gene expression in immortalized human chondrocytes.JCI Insight, 1994
- Adenoviral-mediated gene transfer to rabbit synovium in vivo.JCI Insight, 1993
- The European Spondylarthropathy Study Group Preliminary Criteria for the Classification of SpondylarthropathyArthritis & Rheumatism, 1991