EXCEED THE SPACE PROVIDED. The broad, long-term objective of this proposal is to develop, validate, and employ protein and peptide autoantigen microarrays for profiling autoantibodies found in biological fluids. We will test the hypothesis that large-scale, parallel detection of autoantibody profiles can be used to explore epitope spreading, the role played by a subset of inflammatory cytokines in the initiation and propagation of autoimmunity, and ultimately in selection of antigen-specific tolerizing therapies. We have reduced to practice the use of large- scale arrays to identify autoantibody profiles in many human autoimmune diseases. We will use biochemical, immunological, and molecular biological techniques to validate and extend our ongoing protein array platform in exploring five specific aims in this proposal: (i.) to identify a universal surface chemistry for printing protein, peptide, and ribonucleoprotein complexes; (ii.) to validate autoantibody binding to individual features using highly-characterized serum samples and monoclonal antibodies; (iii.) to construct and validate a comprehensive CTD autoantigen array for detection of autoantibodies; (iv.) to use autoantigen microarrays to characterize serum and tissue-derived autoantibodies from spontaneous and inducible murinc models of SLY; and (v.) to test the hypothesis that autoantibody profiling can be used as a surrogate marker of tolerance in animals treated with antigen-specific, DNA plasmid-bascd, tolerizing vaccines. The results of this proposal may elucidate an expanded role for B lymphocytes and their secreted products in autoimmunity, perhaps heralding an era of customized, antigen- or tissue- specific tolerizing therapy in humans. Moreover, further development of protein microarray technology will have broad applications to the fields of immunology, functional genomics, and proteomics. PERFORMANCE SITE ========================================Section End===========================================

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI051614-03
Application #
6830759
Study Section
Immunological Sciences Study Section (IMS)
Program Officer
Johnson, David R
Project Start
2002-12-15
Project End
2007-11-30
Budget Start
2004-12-01
Budget End
2005-11-30
Support Year
3
Fiscal Year
2005
Total Cost
$361,112
Indirect Cost
Name
Stanford University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
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