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Current CaNIOS Studies

Lupus Nephritis: New Emerging Team (LuNNET)

Glomerulonephritis is a common manifestation of Systemic Lupus Erythematosus (SLE) and a major cause of morbidity and mortality. In order to better understand what distinguishes patients with poor renal outcomes, our goal for this study is to create a national collaborative platform that will unite basic and clinical lupus researchers with expertise in kidney diseases and methodologists. This nation-wide network of experts will pool their unique expertise towards the discovery and definition of the mechanisms that lead to disease expression and damage in lupus nephritis (LN). The creation of a CaNIOS database, with a common dataset including standardized clinical information linked to a centralized biomaterial repository, is central for the success of our Lupus Nephritis New Emerging Team (LuNNET). A process to obtain and collect serum and plasma already exists for GenES and we have linked with members of the Gender and Glomerulonephritis (GN) NET in order to expand our expertise on kidney disease. This will allow us to tap on a well-organized network that is already collecting research specimens from all lupus biopsies performed at the University Health Network (UHN). We will apply a stepwise approach to our experiments. Our first step will be to use frozen renal tissue from a retrospective LN cohort (cohort #1) available at the UHN to generate and test hypotheses. The second step will be to create two prospective cohorts: (1) an inception LN cohort (cohort #2) of 25 SLE patients with new LN, who will be matched with 25 non-LN SLE controls. These individuals will be intensively studied and carefully characterized quarterly for two years and annually thereafter, and (2) a cohort of 200 SLE patients (cohort #3) with either: (i) active LN (100 new or flaring LN), (ii) inactive LN with a previous history of LN (n=50) and (iii) no history of LN (n=50), who will be followed annually with a less intense protocol. Assembly of this centralized dataset will enhance several ongoing projects and the productivity of our researchers, generate new hypotheses to be tested, lead to the identification of modifiable factors associated with a poor outcome, and provide better data on LN in Canada to be shared with clinicians and the public.

Genetic and Environmental factors in Systemic Lupus Erythematosus (GenES Study)

The goal of this research program is to identify genes, environmental factors, and gene-environment interactions that influence the risk of systemic lupus erythematosus (SLE). To this end, we propose to collect and carefully phenotype a large set of SLE cases, together with patients, siblings, and random controls. In this application, we propose the first steps of a long term plan: to collect the families, to test whether defects in apoptosis, cell signaling, DNA repair, and cytokine pathways promote the loss of tolerance that leads to production of antinuclear antibodies, to confirm previously identified environmental associations, and to further the analysis of genes on human chromosome, given the importance of the locus in genetic linkage studies in both human families and mouse models with SLE-related phenotypes. Once this resource has been collected and the confirmatory groundwork completed, then future studies will be able to examine interactions between genes and environmental risk factors, to determine the function of susceptibility genes, and to explore the phenotypic variability.

Learning to Live Better with Lupus: The Health Improvement and Prevention Program (HIPP) in Systemic Lupus Erythematosus

Our goal is to demonstrate that the Health Improvement and Prevention Program (HIPP) will improve health status, decrease cardiovascular risk and improve endothelial function in persons with SLE. We will perform a randomized controlled trail of HIPP versus usual care with a crossover of the usual care group to the HIPP intervention at one year.

The Role of Thrombophilic Factors in Persons with Systemic Lupus Erythematosus (ThromboFIL)

Our goal is to evaluate the risk of thrombosis in persons with systemic lupus erythematosus (SLE) at the time of diagnosis and yearly afterwards, and to evaluate the thrombophilic risk of antiphospholipid antibodies (aPL) in these patients. To achieve the first goal, we will perform a descriptive study of all patients with a new diagnosis of SLE in the past five years seen in the Canadian Network for Improved Outcomes in SLE (CaNIOS) to determine:

  1. the proportion of patients with thrombosis at presentation, and
  2. the rate of thrombotic eventsper person-year afterwards.

To achieve the second goal, we will perform a case-control study using these same patients. Cases will be defined as patients with definite SLE and thrombosis while controls will be matched for centre and disease duration. We will identify two controls for every case.

The 1000 Canadian Faces of Lupus (1000 Faces)

The goal of this research program is to establish a longitudinal multiethnic Canadian cohort of systemic lupus erythematosus (SLE or lupus) patients, to characterize ethnic differences in clinical manifestations and disease outcome, identify socioeconomic, cultural, and environmental factors influencing the course and outcome of lupus in different ethnic groups, and to determine the prognostic value of anti-Smith (anti-Sm) antibody in these patients. We will place particular emphasis on Asian Canadians and First Nations Canadians, as these population groups are both growing rapidly, have genetic links, are more frequently anti-Sm positive, and are generally thought to have more severe lupus. We propose to collect and phenotype >1000 lupus patients from lupus clinics across Canada, with particular efforts to include centres with multiethnic populations. In this application, we propose the first steps of a long-term plan: to collect the patients, phenotype them, (including determination of anti-Sm status), and obtain detailed data on their ethnic origin, socioeconomic (SES), environmental and cultural factors. We will then be able to form a cross-sectional picture of lupus in different ethnicities and determine the contribution of ethnicity and anti-Sm to disease activity, progression, damage, and future mortality in SLE. In future studies we will address long-term outcomes, treatment responses, and access to care issues. Long-term goals include identifying genetic interactions with all of the above factors influencing disease course and outcome in lupus, and developing treatment plans tailored to the different ethnic or serologic groups, based on appropriate risk management strategies.