The members of the University of Colorado Autoimmunity Center of Excellence (Colorado ACE) are proposing two Clinical Projects and one Collaborative Project. The overall Center has been constructed with a focus on two areas. The first is the development of innovative therapeutic strategies, in the Primary Clinical Project with regard to the mechanism of effect of the therapeutic on HLA-peptide interaction in Type 1 Diabetes (T1D) and in the Alternate Clinical Project with regard to the focus on prevention of the onset of clinically apparent disease in Rheumatoid Arthritis (RA). Studies in the Collaborative Project are intended to substantially increase our understanding of the specific immune mechanisms underlying exacerbation and remission of a human disease, neuromyelitis optica, in which the pathogenic process is driven by B and T cell recognition of a well-defined autoantigen, aquaporin 4. In addition, because of recent increases in our understanding of antigen-specific responses in T1D and RA, we will also be able to determine in the Clinical Projects how therapeutic intervention not only affects clinical outcomes but also relevant antigen-specific responses. To address the stated goals, the investigators of the Colorado ACE propose three Specific Aims:
Specific Aim #1 : Evaluate the ability of novel therapeutic strategies designed to interrupt/modulate MHC Class II molecular interactions with peptides to lead to amelioration of organ-specific and non-specific autoimmunity.
Specific Aim #2 : Develop, test and evaluate the immunomodulatory effects and clinical benefit of treatment strategies that are focused on prevention of the clinical onset of rheumatoid arthritis and other autoimmune diseases in extraordinarily high-risk subjects.
Specific Aim #3 : Develop an understanding of the alterations to B and T cell autoantigen-specific responses that are associated with clinical responses to targeted therapeutics and change in clinical status. Finally, with a large and varied clinical population, a strong history of successful clinical studies and trials performed in a highly collaborative manner, and broad experience in clinical phenotyping and biomarker development, the Colorado ACE investigators will provide an important resource to the newly constituted ACE Consortium.

Public Health Relevance

The Colorado Autoimmunity Center of Excellence will develop and evaluate innovative therapies for autoimmune diseases. The focus of the proposed studies is on very early disease, the potential for prevention, and understanding antigen-specific effects of immune modulation as well as the relationship between these biomarkers and clinical status.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project with Complex Structure Cooperative Agreement (UM1)
Project #
Application #
Study Section
Special Emphasis Panel (ZAI1)
Program Officer
Johnson, David R
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Colorado Denver
Internal Medicine/Medicine
Schools of Medicine
United States
Zip Code
Weil, Marie-Theres; Möbius, Wiebke; Winkler, Anne et al. (2016) Loss of Myelin Basic Protein Function Triggers Myelin Breakdown in Models of Demyelinating Diseases. Cell Rep 16:314-22
Herwerth, Marina; Kalluri, Sudhakar Reddy; Srivastava, Rajneesh et al. (2016) In vivo imaging reveals rapid astrocyte depletion and axon damage in a model of neuromyelitis optica-related pathology. Ann Neurol :
Raza, Karim; Klareskog, Lars; Holers, V Michael (2016) Predicting and preventing the development of rheumatoid arthritis. Rheumatology (Oxford) 55:1-3
Deane, Kevin D (2015) Rheumatoid arthritis: Autoantibodies, citrullinated histones and initiation of synovitis. Nat Rev Rheumatol 11:688-9
Owens, Gregory P; Ritchie, Alanna; Rossi, Andrea et al. (2015) Mutagenesis of the aquaporin 4 extracellular domains defines restricted binding patterns of pathogenic neuromyelitis optica IgG. J Biol Chem 290:12123-34
Kowarik, Markus C; Dzieciatkowska, Monika; Wemlinger, Scott et al. (2015) The cerebrospinal fluid immunoglobulin transcriptome and proteome in neuromyelitis optica reveals central nervous system-specific B cell populations. J Neuroinflammation 12:19
Holers, V Michael (2014) Insights from populations at risk for the future development of classified rheumatoid arthritis. Rheum Dis Clin North Am 40:605-20
Finckh, Axel; Deane, Kevin D (2014) Prevention of rheumatic diseases: strategies, caveats, and future directions. Rheum Dis Clin North Am 40:771-85