High Throughput Screening of the Autoimmune Epitome
Principal Investigator: Nancy J Olsen
Abstract: DESCRIPTION (provided by applicant): This application addresses broad Challenge Area (04) Clinical Research and specific Challenge Topic 04-AR-101 Autoimmunity for Diseases of Skin, Joints, Muscles and Other Tissues. It is estimated that approximately 5% of the US population is affected by an autoimmune disorder such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), or multiple sclerosis (MS). These conditions cause considerable morbidity and excess mortality, as well as direct and indirect health care costs in the tens of billions of dollars. The diagnosis of these conditions is often difficult, requiring multiple visits to medical specialists, and the interpretation of imperfect tests. Even when the diagnosis is certain, the tools to offer prognosis or personalize therapy are often lacking. The overall goal of this project is to rapidly and thoroughly evaluate a novel technology for the measurement of antibodies specific for SLE, a model for systemic autoimmunity. The technology is based on the ability of synthetic polymers of N-substituted glycine termed 'peptoids'to serve as specific ligands for immunoglobulin. Two specific aims will be undertaken: 1) Validation of a novel technology platform for IgG biomarker discovery using systemic lupus erythematosus as a model, and 2) Determine the ability of peptoid ligands to identify pre-clinical autoimmunity. To accomplish these aims, highly specific peptoid ligands will be synthesized, purified and attached to fluorescent beads to create a high-throughput screening platform. They will then be used to measure and characterize autoantibodies from subjects with clinically evident SLE as well as those with early or incomplete forms of the disease. Together, the results of this study will lead to the development of new tools for clinicians and clinical researchers to use in the assessment of autoimmune diseases. PUBLIC HEALTH RELEVANCE: Autoimmune diseases are common causes of illness that are difficult to diagnose and monitor. This study will test a completely new method to monitor changes in the composition of the blood of patients with systemic lupus erythematosus. Using this as a model system, it is hoped that other autoimmune diseases will benefit from early diagnosis and treatment.
Funding Period: ----------------2009 - ---------------2011-
more information: NIH RePORT
- Discovery of biomarkers for systemic lupus erythematosus using a library of synthetic autoantigen surrogatesJiexia Quan
Department of Medicine, UT Southwestern Medical Center, Dallas, TX 75390, USA The Department of Immunology, UT Southwestern Medical Center, Dallas, TX 75390, USA The Department of Psychiatry, UT Southwestern Medical Center, Dallas, TX 75390, USA
J Immunol Methods 402:23-34. 2014..These results show that the measurement of IgG binding to peptoids can identify subjects with high levels of pathogenic autoantibodies. ..