Abstract

Diverse initial stimuli may contribute to the pathogenesis of Rheumatoid Arthritis (RA). However, B cell activation and autoantibody production constitutes essential steps in the progression of RA. To address possible mechanisms leading to the induction of autoantibodies in RA, we propose to analyze disease progression in a new model for systemic autoimmunity. This model was derived by constructing homozygous deletion mutants in three structurally related tyrosine kinase receptors, Mer, Ax1, and Tyro3. The following experiments are proposed: 1. Isolate hybridomas from Mer, Ax1, and Tyro3 triple deletion homozygous mice. 2. Characterize the binding and immunoglobulin V gene sequences of autoantibodies directed against collagen type II, glucose-6-phosphate isomerase (GPI), and apoptotic cells. 3. Explore the pathogenic potential of selected autoantibodies by transferred purified monoclonal IgG autoantibodies into naive animals. The analysis of the proposed experiments will guide subsequent steps toward securing extramural funding for studies of antibody-mediated joint erosion.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Center Core Grants (P30)
Project #
5P30AR047379-02
Application #
6664115
Study Section
Special Emphasis Panel (ZAR1)
Project Start
2002-09-01
Project End
2006-08-31
Budget Start
Budget End
Support Year
2
Fiscal Year
2002
Total Cost
Indirect Cost

  Institution

Name
University of Tennessee Health Science Center
Department
Type
DUNS #
941884009
City
Memphis
State
TN
Country
United States
Zip Code
38163

  Publications

Hasty, Karen A; Cho, Hongsik (2016) Stem Cell Considerations for the Clinician. Phys Med Rehabil Clin N Am 27:855-870
Qian, Zhaohui; Latham, Kary A; Whittington, Karen B et al. (2013) Engineered regulatory T cells coexpressing MHC class II:peptide complexes are efficient inhibitors of autoimmune T cell function and prevent the development of autoimmune arthritis. J Immunol 190:5382-91
Qian, Zhaohui; Latham, Kary A; Whittington, Karen B et al. (2010) An autoantigen-specific, highly restricted T cell repertoire infiltrates the arthritic joints of mice in an HLA-DR1 humanized mouse model of autoimmune arthritis. J Immunol 185:110-8
Xing, Zhiqing; Schwab, Luciana P; Alley, Carie F et al. (2008) Titanium particles that have undergone phagocytosis by macrophages lose the ability to activate other macrophages. J Biomed Mater Res B Appl Biomater 85:37-41
Ye, Zhaoyang; Houssein, Houssam S Hajj; Mahato, Ram I (2007) Bioconjugation of oligonucleotides for treating liver fibrosis. Oligonucleotides 17:349-404
Xing, Zhiqing; Hasty, Karen A; Smith, Richard A (2007) Administration of pamidronate alters bone-titanium attachment in the presence of endotoxin-coated polyethylene particles. J Biomed Mater Res B Appl Biomater 83:354-8
Yi, Ae-Kyung; Yoon, Hyunsook; Park, Jeoung-Eun et al. (2006) CpG DNA-mediated induction of acute liver injury in D-galactosamine-sensitized mice: the mitochondrial apoptotic pathway-dependent death of hepatocytes. J Biol Chem 281:15001-12
Rosloniec, Edward F; Brandstetter, Tilmann; Leyer, Sigmar et al. (2006) Second-generation peptidomimetic inhibitors of antigen presentation effectively treat autoimmune diseases in HLA-DR-transgenic mouse models. J Autoimmun 27:182-95
Carbone, L D; Warrington, K J; Barrow, K D et al. (2006) Pamidronate infusion in patients with systemic sclerosis results in changes in blood mononuclear cell cytokine profiles. Clin Exp Immunol 146:371-80
Rosloniec, Edward F; Ivey 3rd, Robert A; Whittington, Karen B et al. (2006) Crystallographic structure of a rheumatoid arthritis MHC susceptibility allele, HLA-DR1 (DRB1*0101), complexed with the immunodominant determinant of human type II collagen. J Immunol 177:3884-92

Showing the most recent 10 out of 24 publications