title: B-cell delivered gene transfer of human S-Ag-Ig fusion protein protects from experimental autoimmune uveitis.
abstract: Uveitis is an important autoimmune disease affecting an estimated 2.3 million Americans. This disease is manifested by inflammation of the retina mediated by the infiltration of T lymphocytes that recognize "S-Antigen" (S-Ag). Current therapies involve the life-long use of immunosuppressive drugs, including steroids. The ability to induce specific tolerance to S-Ag would be desirable and allow patients to be weaned off of steroid therapy. In this study, we determined that S-Ag-Ig retroviral vector was capable of preventing EAU (experimental autoimmune uveoretinitis) in Lewis rats induced by immunization with bovine S-Ag (BoS-Ag). Importantly, B-cell delivered gene therapy with S-Ag-Ig can ameliorate ongoing EAU when the treatment was initiated after rats had been immunized. Furthermore, we have successfully induced tolerance in HLA-DR3 transgenic mice with respect to the T-cell proliferative response. These results demonstrate proof of principle for future efforts to develop this approach for clinical application in patients with uveoretinitis.
authors.affiliation: TolerGenics, Inc. 9610 Medical Center Dr. Suite 230, Rockville, MD 20850, USA. liang@tolergenics.com
authors.forename: Wei
authors.initials: W
authors.lastname: Liang
authors.forename: Zaruhi
authors.initials: Z
authors.lastname: Karabekian
authors.forename: Mary
authors.initials: M
authors.lastname: Mattapallil
authors.forename: Qihong
authors.initials: Q
authors.lastname: Xu
authors.forename: Angelia M
authors.initials: AM
authors.lastname: Viley
authors.forename: Rachel
authors.initials: R
authors.lastname: Caspi
authors.forename: David W
authors.initials: DW
authors.lastname: Scott
mesh_terms: D000818:Animals; D019393:Arrestin / Q000235:genetics* / Q000276:immunology; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology / Q000637:transplantation*; D004195:Disease Models, Animal; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D007108:Immune Tolerance; D007074:Immunoglobulin G / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D051381:Rats; D011917:Rats, Inbred Lew; D011993:Recombinant Fusion Proteins / Q000235:genetics* / Q000276:immunology; D016896:Treatment Outcome; D014605:Uveitis / Q000276:immunology / Q000628:therapy*
chemical_list: D019393:Arrestin; D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins