Systemic lupus erythematosus (SLE) is a devastating autoimmune disease marked by the production of autoantibodies, anti-Smith (Sm) being the most specific for the disease. The etiology of SLE is known to have significant genetic and environmental components. Abundant data link deficiencies of the complement system to the development of autoimmune diseases, particularly SLE. Deficiencies of either complement protein C4 or the complement receptor CR2 (CD21) trigger development of SLE-like disease in mice. Partial or complete C4 deficiency strongly predisposes to SLE in humans, and recently, decreased CD21 expression has been observed in human SLE patients. How these genetic deficiencies in complement interact with environmental effectors to trigger disease is unknown. We have crossed mice deficient for C4 or CD21 to a transgenic line which expresses an Ig heavy-chain specific for Sm. We propose to study the effect of environmental stressors on anti-Sm B cells and the development of anti-Sm antibodies in these mice to elucidate the interplay between genetic and environmental components of SLE development. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
5F30ES014519-02
Application #
7163455
Study Section
Special Emphasis Panel (ZRG1-F07 (20))
Program Officer
Humble, Michael C
Project Start
2006-01-01
Project End
2008-12-31
Budget Start
2007-01-01
Budget End
2007-12-31
Support Year
2
Fiscal Year
2007
Total Cost
$28,048
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Nicholas, Matilda W; Dooley, Mary Anne; Hogan, Susan L et al. (2008) A novel subset of memory B cells is enriched in autoreactivity and correlates with adverse outcomes in SLE. Clin Immunol 126:189-201