Sjogren's syndrome (SS) is a clinical and scientific challenge. This application will focus on the role of B cells n this disorder, because B cells seem to play a key role in the pathogenesis of the illness and because B cell directed therapy for SS and related disorders is an important new approach. The broad goal is to exploit a new SS murine model to isolate the role of the B cell in SS. We will characterize B cell subsets in diseased tissue compare their repertoire to peripheral B cells using molecular genetic techniques. We will develop means of depleting B cells in vivo using monoclonal antibodies so that we will have a model of human SS B cell depletion (currently in clinical trials), and will examine the B-cell repertoire during reconstitution of depleted animals. Finally, we will develop in vivo B-cell imaging techniques in SS mice to study real-time trafficking of B cells. These methods may prove useful to monitor disease activity and therapy in humans with SS and related conditions. The research is relevant to the agency mission of understanding and treating this important autoimmune disorder.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
3R01DE017590-04S2
Application #
7912258
Study Section
Special Emphasis Panel (ZDE1-YL (33))
Program Officer
Burgoon, Penny W
Project Start
2006-08-01
Project End
2011-05-31
Budget Start
2009-06-01
Budget End
2010-05-31
Support Year
4
Fiscal Year
2009
Total Cost
$131,213
Indirect Cost
Name
Temple University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
057123192
City
Philadelphia
State
PA
Country
United States
Zip Code
19122
Singh, Namrata; Traisak, Pamela; Martin, Kayla A et al. (2014) Genomic alterations in abnormal neutrophils isolated from adult patients with systemic lupus erythematosus. Arthritis Res Ther 16:R165
Chen, David R; Cohen, Philip L (2012) Living life without B cells: is repeated B-cell depletion a safe and effective long-term treatment plan for rheumatoid arthritis? Int J Clin Rheumtol 7:159-166
Jog, Neelakshi R; Frisoni, Lorenza; Shi, Qin et al. (2012) Caspase-activated DNase is required for maintenance of tolerance to lupus nuclear autoantigens. Arthritis Rheum 64:1247-56
Singh, Namrata; Cohen, Philip L (2012) The T cell in Sjogren's syndrome: force majeure, not spectateur. J Autoimmun 39:229-33
Shao, Wen-Hai; Zhen, Yuxuan; Finkelman, Fred D et al. (2012) Intrinsic unresponsiveness of Mertk-/- B cells to chronic graft-versus-host disease is associated with unmodulated CD1d expression. J Autoimmun 39:412-9
Meng, Wenzhao; Li, Yongmei; Xue, Emily et al. (2012) B-cell tolerance defects in the B6.Aec1/2 mouse model of Sjögren's syndrome. J Clin Immunol 32:551-64
Meng, Wenzhao; Yunk, Lenka; Wang, Li-San et al. (2011) Selection of individual VH genes occurs at the pro-B to pre-B cell transition. J Immunol 187:1835-44
Shao, Wen-Hai; Cohen, Philip L (2011) Disturbances of apoptotic cell clearance in systemic lupus erythematosus. Arthritis Res Ther 13:202
Luning Prak, Eline T; Monestier, Marc; Eisenberg, Robert A (2011) B cell receptor editing in tolerance and autoimmunity. Ann N Y Acad Sci 1217:96-121
Shao, Wen-Hai; Kuan, Anita P; Wang, Charlie et al. (2010) Disrupted Mer receptor tyrosine kinase expression leads to enhanced MZ B-cell responses. J Autoimmun 35:368-74

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