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Identification of Serologic Biomarkers in Sarcoidosis

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R43AI092886-01
Agency Tracking Number: R43AI092886
Amount: $301,893.00
Phase: Phase I
Program: SBIR
Solicitation Topic Code: NIAID
Solicitation Number: PA10-050
Solicitation Year: 2011
Award Year: 2011
Award Start Date (Proposal Award Date): N/A
Award End Date (Contract End Date): N/A
Small Business Information
BOSTON, MA 02118-
United States
DUNS: 126775860
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 (617) 638-5243
Business Contact
Phone: (617) 636-5422
Research Institution

DESCRIPTION (provided by applicant): This project's long-term goal is the development and clinical validation of a useful diagnostic blood test for the disease sarcoidosis. Sarcoidosis is an inflammatory disorder characterized by granulomas, most commonlyin the lungs. Its cause is unknown. The diagnosis of sarcoidosis is currently one of exclusion; there is no reliable, affirmative, rule-in, diagnostic test. Namely, the patientlt s symptoms often result in a chest x-ray, which leads to a biopsy showing non-caseating granulomas. Other potential causes, such as TB or exposure to beryllium, are excluded, thereby leading to a diagnosis of sarcoidosis. Our goal is a blood diagnostic test that affirmatively indicates sarcoidosis. This project is also a first reduction to practice for a newly developed discovery platform for identifying new serologic assay targets. The principle of the approach is that inflammatory disorders cause the production of serum antibodies. Identifying these disease-associated antibodies (in diseases of unknown etiology) could be of enormous value. The previously difficult hurdle has been that characterization of antibody immunoreactivity requires the antigen. In sarcoidosis, the antigen is unknown. Consequently, we used a random peptidecombinatorial library displayed on bacteriophage in lieu of antigen. We established a method for identifying peptides (from the library) that are immunoreactive with patient antibodies but not with serum antibodies from a reference group. This kind of differential library enrichment using polyclonal serum antibodies has previously been challenging. There are two Specific Aims: (1) Sensitivity and specificity analysis of the candidate peptide targets (displayed on phage), and (2) Final assay design validation. In Aim 1, we will test the (gt100 already identified) candidate peptide phage, to determine their sensitivity and specificity in the diagnosis of sarcoidosis. Our Preliminary Data shows that these peptides are immunoreactive with at least some sarcoidosis sera, and not with normal control sera or sera from PPD+ individuals. We will analyze the immunoreactivity of each peptide with at least 58 sarcoidosis sera and gt110 control sera. The sera are provided through a consortium of clinical collaboratorsat Tufts Medical Center, Boston University Medical Center, and Vanderbilt University Medical Center. In Aim 2, we will combine the best- performing peptides into a single immunoassay, for superior sensitivity. In addition to sensitivity and specificity, we will also evaluate precision, linearity, and assay stability. In a future Phase II, we will conduct a prospective study, with an independent set of patients, for regulatory submission. PUBLIC HEALTH RELEVANCE: This project is for the purpose of creating a blood test for sarcoidosis, a disease of unknown cause and for which there is no definitive test. The new technology that we employed to discover the immune response targets for this test is applicable to many other diseases involving the bodylt s immune system.

* Information listed above is at the time of submission. *

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