The proposed effort aims to change the paradigm of medical diagnostics based upon antibody biomarkers, enabling diagnosis of hundreds of prevalent diseases and conditions using a single inexpensive test. Although antibodies presently serve as excellent biomarkers for several diseases, seldom are more than a few antibody specificities assessed in a single test. Furthermore, most current tests that measure antibody biomarkers typically do not provide sufficient diagnostic sensitivity and specificity when used alone. To address these problems, the specificities of a broad spectrum of the circulating antibody repertoire will be profiled simultaneously, using a novel integrated discovery and array construction process based upon living reagents. To demonstrate the intrinsic power and potential broad applicability of this approach, we will generate and clinically validate the utility of expandable antibody repertoire profiling microarrays for diagnosis, prognostication, and therapeutic monitoring of Celiac Disease. Using high-resolution antibody specificity data, novel self- and non-self antigens will be identified as the targets of serum antibodies that may be involved in disease onset or progression. Application of the antibody detection reagent discovery process to a large number of disease cohorts from multiple national centers will enable establishment of the human antibody specificity repertoire database, providing a broadly applicable tool to better understand disease etiology and personalize therapy for Celiac and other diseases. Success of this effort will reduce the cost of diagnostic tests and the economic burden of undiagnosed and misdiagnosed disease.

Public Health Relevance

The objective of the proposed project is to develop a general and scalable methodology to rapidly and economically profile the specificities of the repertoire of patient antibodies in a massively parallel format to diagnose disease. This new technology will first be applied to develop a improve diagnosis, early detection of Celiac Disease as well as to enable risk prognostication and therapeutic monitoring of patients. The method could then be directly extended to create low-cost diagnostic tools for a broad range of diseases for which current diagnostic technology is lacking. )

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI092204-03
Application #
8414834
Study Section
Cellular and Molecular Immunology - A Study Section (CMIA)
Program Officer
Rothermel, Annette L
Project Start
2011-01-15
Project End
2015-12-31
Budget Start
2013-01-01
Budget End
2013-12-31
Support Year
3
Fiscal Year
2013
Total Cost
$292,327
Indirect Cost
$55,212
Name
University of California Santa Barbara
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
094878394
City
Santa Barbara
State
CA
Country
United States
Zip Code
93106
Spatola, B N; Kaukinen, K; Collin, P et al. (2014) Persistence of elevated deamidated gliadin peptide antibodies on a gluten-free diet indicates nonresponsive coeliac disease. Aliment Pharmacol Ther 39:407-17
Elliott, Serra E; Parchim, Nicholas F; Liu, Chen et al. (2014) Characterization of antibody specificities associated with preeclampsia. Hypertension 63:1086-93
Ballew, John T; Murray, Joseph A; Collin, Pekka et al. (2013) Antibody biomarker discovery through in vitro directed evolution of consensus recognition epitopes. Proc Natl Acad Sci U S A 110:19330-5