Overview
Recent Publications
Robinson WH, Steinman L, Utz PJ. Proteomics technologies for the study of autoimmune disease. Arthritis Rheum. 2002. 46:885-93.
Robinson WH, Steinman L, Utz PJ. Protein and peptide array analysis of autoimmune disease. Biotechniques. 2002. 66-9.
Robinson WH, Garren H, Utz PJ, Steinman L. Millennium Award. Proteomics for the development of DNA tolerizing vaccines to treat autoimmune disease. Clin Immunol. 2002. 103:7-12. Review.
Our objective is to develop and apply planar antigen arrays to profile the specificity and isotype usage of autoantibody responses in biological specimens.
We are developing spotted antigen arrays that contain thousands of proteins and peptides attached to the surface of derivatized microscope slides in ordered arrays where they can be analyzed for their interactions with autoantibodies. We demonstrated the feasibility of this approach by applying first-generation 'connective tissue disease' (CTD) arrays to profile autoantibody responses in human SLE and RA, and 'myelin proteome' arrays to study, develop therapies for, and monitor therapeutic responses in, an animal model for multiple sclerosis (MS).
We anticipate that proteomic monitoring of blood autoantibody responses will revolutionize care for patients with autoimmune disease by enabling identification of 'biosignatures' for diagnosis, prognostication, and guiding therapy.
Rationale:
Despite significant research efforts, the etiology of and self-molecules targeted in the vast majority of autoimmune diseases, including systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), remain poorly understood. The production of high-affinity autoantibodies is a hallmark of autoimmune disease, and for SLE and RA specific autoantibodies are associated with disease subsets and are predictive of future disease manifestations. To date, simultaneous profiling of autoantibody responses against large panels of candidate autoantigens has not been performed due to lack of enabling technologies, such as antigen arrays.
We are developing and applying antigen arrays to enable large-scale characterization of immune responses against self-proteins, and represent a powerful and promising strategy to identify self-proteins involved in the initiation and progression of autoimmune disease. Knowledge of autoimmune self-protein targets could provide insights into the etiology of autoimmune diseases, and will enable development of diagnostic and prognostic tests as well as more effective tolerizing therapies.
Our goals for the Proteomics Center include:
- To profile autoantibody responses for diagnosis.
- To characterize the evolution of autoantibody profiles for prognostication and monitoring therapy: analysis of autoantibody specificity and isotype usage.
- To discover and characterize novel autoantigens.
- To develop, select and monitor antigen-specific tolerizing therapies.
