This is a proposal to establish a Center of Excellence for Autoimmunity at the University of Pennsylvania School of Medicine. The presence of a strong basic science of immunology on the campus, combined with a long-standing standard of excellence in the management of patients with various autoimmune disorders at the Hospital of the University of Pennsylvania, makes Penn the idea place for this Center. The clinical component of the Center consists of three clinical trials: (1) a Phase I/II trial on the use of antibody to Interleukin-12 for the treatment of multiple sclerosis; 2) a Phase I/II trial on the use of Interleukin 12 in the treatment of inflammatory bowel disease; 3) use of anti-CD20 antibody for the treatment of systemic lupus erythematosus. The basic science component is focused on the elucidation of the basic mechanisms of autoimmunity and immunomodulation related to the clinical trial. Project 3 studies the role of Il-12 in the pathogenesis and therapy of multiple sclerosis and its animal counterpart, experimental autoimmune encephalomyelitis. Project 4 focuses on the mechanisms of anti-B cell therapy in systemic lupus erythematosis and its murine model. The Center has two cores-an immunology core to centralize the immunological tests required in all projects, and an administrative core for administration of the Center and facilitation of interaction between clinicians and basic scientists involved in the different projects.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI046358-02
Application #
6170704
Study Section
Special Emphasis Panel (ZAI1-EWS-I (S1))
Program Officer
Collier, Elaine S
Project Start
1999-09-28
Project End
2003-08-31
Budget Start
2000-09-01
Budget End
2001-08-31
Support Year
2
Fiscal Year
2000
Total Cost
$862,148
Indirect Cost
Name
University of Pennsylvania
Department
Neurology
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Choudhury, Arpita; Cohen, Philip L; Eisenberg, Robert A (2010) B cells require ""nurturing"" by CD4 T cells during development in order to respond in chronic graft-versus-host model of systemic lupus erythematosus. Clin Immunol 136:105-15
Li, Yongmei; Chen, Fangqi; Putt, Mary et al. (2008) B cell depletion with anti-CD79 mAbs ameliorates autoimmune disease in MRL/lpr mice. J Immunol 181:2961-72
Tsao, Patricia Y; Jiao, Jing; Ji, Mei Qing et al. (2008) T cell-independent spontaneous loss of tolerance by anti-double-stranded DNA B cells in C57BL/6 mice. J Immunol 181:7770-7
Ma, Zhongjie; Choudhury, Arpita; Kang, Sun-Ah et al. (2008) Accelerated atherosclerosis in ApoE deficient lupus mouse models. Clin Immunol 127:168-75
Albert, D; Dunham, J; Khan, S et al. (2008) Variability in the biological response to anti-CD20 B cell depletion in systemic lupus erythaematosus. Ann Rheum Dis 67:1724-31
Choudhury, Arpita; Cohen, Philip L; Eisenberg, Robert A (2007) Mature B cells preferentially lose tolerance in the chronic graft-versus-host disease model of systemic lupus erythematosus. J Immunol 179:5564-70
Guan, Yangtai; Shindler, Kenneth S; Tabuena, Philomela et al. (2006) Retinal ganglion cell damage induced by spontaneous autoimmune optic neuritis in MOG-specific TCR transgenic mice. J Neuroimmunol 178:40-8
Ma, Zhongjie; Chen, Fangqi; Madaio, Michael P et al. (2006) Modulation of autoimmunity by TLR9 in the chronic graft-vs-host model of systemic lupus erythematosus. J Immunol 177:7444-50
Shindler, Kenneth S; Guan, Yangtai; Ventura, Elvira et al. (2006) Retinal ganglion cell loss induced by acute optic neuritis in a relapsing model of multiple sclerosis. Mult Scler 12:526-32
Choudhury, Arpita; Maldonado, Michael A; Cohen, Philip L et al. (2005) The role of host CD4 T cells in the pathogenesis of the chronic graft-versus-host model of systemic lupus erythematosus. J Immunol 174:7600-9

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