Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease. It affects multiple systems. The disease causes considerable morbidity and mortality. Despite considerable progress in our understanding of this disease, its pathogenesis remains to be elucidate. It is well documented that both genetic and environmental factors play important roles in this disorder. It is postulated that molecular mimics may initiate an autoimmune response. The diversification of the autoimmune response with inflammation leads to end organ damage in appropriate hosts. The University of Virginia Specialized Center of Research on SLE is being established to facilitate a multidisciplinary approach to study this disease with a special emphasis on the immunological and genetic basis for it pathogenesis. The SCOR is strengthened by forming consortiums with Mayo Clinic and John Hopkins Hospital, which will provide expertise in mouse genetics, transgenic mice expressing DR and DQ antigens and the Hopkins Lupus Cohort for the proposed clinical investigation. The SCOR has four projects and three cores. The projects are 1) HLA-DR and DQ antigens in SLE-related Autoimmunity, 2) Role of T cells in Murine SLE, 3) Genetic Control of Autoimmunity in Lupus-Prone Mice and 4) Autoantibody Diversification in SLE Flares. The proposed studies are to provide experimental evidence to support the state hypothesis. The three cores are: 1) Administration Core, 2) Cell Sciences and Immunochemistry Core and 3) The Mouse Genetic Core. These cores will serve all the projects and will facilitate interactions among investigators within the UVA SCOR on SLE. The SCOR represents both inter- and intra-institutional collaborations. The interactive approach will provide new insights into the immunological and genetic factors important in SLE and may provide a rational basis for novel therapy.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Specialized Center (P50)
Project #
3P50AR045222-03S1
Application #
6324105
Study Section
Special Emphasis Panel (ZAR1 (J2))
Program Officer
Freeman, Julia B
Project Start
1998-07-01
Project End
2002-06-30
Budget Start
2000-07-01
Budget End
2001-06-30
Support Year
3
Fiscal Year
2000
Total Cost
$38,459
Indirect Cost
Name
University of Virginia
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
001910777
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
Sung, Sun-Sang J; Ge, Yan; Dai, Chao et al. (2017) Dependence of Glomerulonephritis Induction on Novel Intraglomerular Alternatively Activated Bone Marrow-Derived Macrophages and Mac-1 and PD-L1 in Lupus-Prone NZM2328 Mice. J Immunol 198:2589-2601
Dai, Chao; Deng, Yun; Quinlan, Aaron et al. (2014) Genetics of systemic lupus erythematosus: immune responses and end organ resistance to damage. Curr Opin Immunol 31:87-96
Ge, Yan; Jiang, Chao; Sung, Sun-Sang J et al. (2013) Cgnz1 allele confers kidney resistance to damage preventing progression of immune complex-mediated acute lupus glomerulonephritis. J Exp Med 210:2387-401
Lewis, Janet E; Fu, Shu Man; Gaskin, Felicia (2013) Autoimmunity, end organ damage, and the origin of autoantibodies and autoreactive T cells in systemic lupus erythematosus. Discov Med 15:85-92
Ge, Yan; Brown, Michael G; Wang, Hongyang et al. (2012) Genetic approach to study lupus glomerulonephritis. Methods Mol Biol 900:271-90
Fu, Shu Man; Deshmukh, Umesh S; Gaskin, Felicia (2011) Pathogenesis of systemic lupus erythematosus revisited 2011: end organ resistance to damage, autoantibody initiation and diversification, and HLA-DR. J Autoimmun 37:104-12
Deshmukh, Umesh S; Sim, Davis L; Dai, Chao et al. (2011) HLA-DR3 restricted T cell epitope mimicry in induction of autoimmune response to lupus-associated antigen SmD. J Autoimmun 37:254-62
Jiang, Chao; Deshmukh, Umesh S; Gaskin, Felicia et al. (2010) Differential responses to Smith D autoantigen by mice with HLA-DR and HLA-DQ transgenes: dominant responses by HLA-DR3 transgenic mice with diversification of autoantibodies to small nuclear ribonucleoprotein, double-stranded DNA, and nuclear antigens. J Immunol 184:1085-91
Sharma, Rahul; Sung, Sun-sang Joe; Fu, Shu Man et al. (2009) Regulation of multi-organ inflammation in the regulatory T cell-deficient scurfy mice. J Biomed Sci 16:20
Bagavant, Harini; Fu, Shu Man (2009) Pathogenesis of kidney disease in systemic lupus erythematosus. Curr Opin Rheumatol 21:489-94

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