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Symposium Chairs
Dr. Katherine A. Siminovitch
Professor, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto
Dr. Eleanor Fish
Professor, Department of Immunology, University of Toronto
Symposium Organized by
CIHR Institute of Infection and Immunity
Dr. Bhagirath Singh, Scientific Director
Symposium Co-sponsored by
CIHR Institutes of Aging, Gender and Health, Nutrition, Metabolism and Diabetes
I: Autoimmune Diseases: Basic Mechanisms and Commonalities
II: Immunological Principles
III: Science and Technology Platforms
IV: US National Institute of Allergy and Infectious Diseases
Conference Recommendations
Conclusion
The research symposium Integrating Discovery Platforms in Autoimmune Diseases aimed to develop a framework for a Canadian health research agenda in autoimmune diseases by targeting the following objectives: to explore the current situation in autoimmune diseases, and in particular basic mechanisms leading to, and commonalities among, these diseases; to identify strategic directions and potential research questions to be used, for example, as the basis for CIHR and partner-sponsored Requests for Applications and for integration of autoimmune diseases into the Canadian Lifelong Health Initiative; and to enhance collaboration and partnerships among stakeholders in the autoimmune diseases community.
The presentations informed participants on the current situation in autoimmune research and set a framework for discussions related to strategic planning.
Session I: Autoimmune Diseases: Basic Mechanisms and Commonalities
 Dr. John A. Wilkins of Manitoba Centre for Proteomics and Dr. Hani El-Gabalaway of the University of Manitoba |
Session II: Immunological Principles
 Dr. Daniel Rotrosen of the National Institute of Allergy and Infectious Diseases, National Institutes of Health and Dr. Stephen D. Miller from Northwestern University |
Session III: Science and Technology Platforms
Dr. Steve Collins and Dr. Pere Santamaria co-chaired Session III. The session opened with a presentation by Dr. Claire Bombardier (in association with Dr. Sheilah Hogg-Johnson), of the Toronto General Research Institute, who used the example of rheumatoid arthritis to illustrate Epidemiological Prognostic Models. She discussed classic predictors of disease outcome; disease activity at presentation, spread in terms of structural damage; functional ability; and variables such as socio-economic status apart from biological factors that have impact on disease outcome. Dr. John A. Wilkins from the Manitoba Centre for Proteomics presented three specific examples of The Application of Proteomics to the Study of Human Disease and discussed issues related to patient selection and sample acquisition, remarking that our proteomic capabilities are rapidly increasing. Dr. Alexandre Montpetit, of McGill University and the Genome Quebec Innovation Centre, spoke about Emerging Genomic Tools to Study Autoimmune and Other Complex Diseases. He noted that the phenotype associated with a given disease and the underlying genetic defect can be studied by linkage analysis or association; however, due to the large size of the human genome, linkage analysis is more appropriate for mapping on a genomic scale. Dr. Igor Jurisica, University of Toronto and Queen's University, presented Towards an Integrated and Intelligent Molecular Medicine, discussing the computational aspects, challenges and possibilities that high throughput data obtained from microarray and protein array analyses afford in the characterization of complex diseases.
Session IV: US National Institute of Allergy and Infectious Diseases
Dr. Jack P. Antel chaired the final session in which Dr. Daniel Rotrosen, of the National Institutes of Health, USA, presented an overview of NIAID/NIH Funding and Strategic Planning as Related to Autoimmune Disease. In the 2003 fiscal year the NIH awarded an estimated $591 million dollars for autoimmunity research, which represents about 2.2% of the $27 billion dollar NIH budget. Approximately 45% of the autoimmunity expenditures are in projects examining pathogenesis and immune dysfunction, while 3% of the funds are allocated to the development of new animal models. The ultimate goal of the NIH's clinical research programs is to bring new vaccines, immune-based therapies and diagnostics to clinical practice.
Supports, Opportunities and Challenges
Following the presentations, participants worked in small, mixed groups to discuss the following two issues with the goal of selecting strategic research directions. Some groups noted overlap between these two areas. The following is a summary of the discussions.
 Dr. Terry L. Delovitch of the Robarts Research Institute and Dr. Luanne Metz from the University of Calgary |
|
New Research Questions |
Supports Required | |
| Methods for Early Case Findings | Benefits and drawbacks of doing direct-to-consumer advertising to generate cases, including analysis of retrieval numbers and false positives. Value of billing databases in identifying early diagnosis. Benefits of networks with general practitioners to identify early cases, e.g., through continuing medical education. |
|
| Biometrics |
Development of a clean, standardized, agreed-upon set of common variables for the determinants of health. Methods for cohort research, e.g., statistical analysis for innovative data mining of biometrics, patterns of care, patient outcomes. Innovative study designs, e.g., crossover designs with strategies for selecting control groups. Common, across-disease, early case definitions and innovative statistical methods for grouping clusters of early disease classifications. |
|
| Cohort Methodologies |
Innovative data collection methods that facilitate participation and retention, e.g., data collection that is integrated into practice, with value added for participating clinicians and applications to community practice. Research into methods for addressing practical issues related to cohort retention and follow-up, e.g., what to do when patients change physicians or move to another province, incentives for patients to remain involved in data collection processes. Issues related to methods of targeted sampling, e.g., to achieve community representation or to support standard tissue collection across various sites. Investigator-initiated research questions, e.g., on courses and prognosis of patients. |
Supports are required to ensure that the research questions in this and the two following sections are addressed. A top priority in terms of capacity development involves the creation of a funded standing group or superstructure that enables integrated approaches among autoimmune disease researchers. Clinical researchers in autoimmune disease face many similar problems across Canada, both within individual diseases and across diseases. The purpose of this standing group would be to identify, clarify and address issues such as information technology, bar codes, privacy, data security, standards for tissue collection and handling, innovative methods for data collection and access to billing data. |
| Tissue Regeneration and Repair |
Mobilization of progenitor cells to enhance repair. Manipulation of pre-existent cells to promote down regulation of cytopathic receptors, or upregulation of growth receptors. Molecular response during damage, recovery, repair and remodeling. The process of tissue response to damage (fibrosis, gliosis), when it ceases to be beneficial and becomes detrimental to repair. |
Effective collaboration and cohesion among the agendas of hospitals, research institutes, universities, as well as public and private funding agencies. Coordinated access to relevant tissues to optimize research. Rational integration of the multiple federal programs in existence to facilitate and optimize hiring practices and initiation of research. |
| Biomarkers |
Biomarker identification and validation (risk, activity, progression, response to drugs, and disease). Development and implementation of biomarkers and bioassays in well-designed clinical trials. Hyper-accelerated progression of biomarkers in clinical trials. Tissue- and species-specific biomarkers. Population-based studies involving the building of new, early cohorts to identify/develop biomarkers. Interface with chemical genomics - array data (gene) and screen library. Imaging biomarkers including molecular biomarkers for in vivo imaging of target organs. Development of methodology for dealing with large data sets that are unique to Autoimmune Diseases (AID). |
There is a need for infrastructure and core facilities and the development of national consortia to enable integrated approaches to AID that can minimize duplication among the agencies involved.
|
| Immunopatho-genesis |
Exploring regulatory pathways for treatment from the genetics to expression and function. Immunotherapies that alter and cure disease. Correlate lessons learned from oncology. |
Capacity building through training and recruiting. Exploration of linkages to established immune tolerance networks. |
| Functional Genomics |
How to validate the functional impact of genetic polymorphisms identified in human or animal models. How to harness outputs of large-scale genomic/proteomic data sets to translate to molecular phenotype and pathophysiology of disease. Genetic regulation of pre-clinical phenotypes (based on biomarkers). |
Organizational infrastructure for a data coordinating centre, including financial administration, communication between research centres, information and ready access to core facilities for genomics, proteomics, imaging. Sustained funding adequate to allow new teams to organize, establish platforms, produce data and take the risks required for innovation. |
| Microbial Autoimmune Pathogenesis |
Construction of new animal models of autoimmune disease (including non-GI) using proscribed infections with well-defined microbial constituents. Looking at responses to infection and products of replicated fetal/immediate newborn in a gnotobiotic controlled environment. Determinants of immunoreactivity throughout life. Translation to human neonatal physiology/biology imprinting |
Gnotobiotic facilities for experimental animals. Data bases, e.g., mining and construction of appropriate questions. Cryopreservation of animal models for interprovincial transfer. Free availability of new animal models. Viral/microbial bank. |
Drs. Siminovitch, Finegood and Singh each addressed the participants with closing remarks, emphasizing the importance of the meeting as a foundation for developing new research initiatives on integrated discovery platforms. Dr. Singh confirmed the cross-cutting nature of autoimmune diseases and the need to have Voluntary Health Organizations (VHO) involved in the development and implementation of research frameworks. He also acknowledged the benefits of having VHO representatives at the symposium and referred to their remarks on the second afternoon, when VHO participants emphasized the importance of inclusive, collaborative approaches to research that would result in clear health outcomes for both patients and caregivers. He further noted the presence of researchers across the four CIHR themes and the importance of following through on new relationships developed at this session. He will be sharing the results of the workshop with all parties in attendance, and will also be holding further discussions with the NIH to follow through on suggestions made regarding possible long-term infrastructure partnerships.
