Spotlight on Canadian Research
As part of Lupus Canada’s initiatives to support research and educate Canadians as to the important work researchers are conducting we are pleased to share with you our Spotlight on Canadian Research in the field of lupus. We hope you find this content informative. We strive to update the content on a regular basis so that we can provide you with the most up-to-date, relevant information as it pertains to lupus.
Non-pharmacological interventions to improve the socioeconomic lives of individuals with SLE
Principal: Dr. Ann Clarke
Team members: Dr. Susan Elliott, Dr. Francesca Cardwell, Dr. May Choi, Dr. Elijah Bisung, Dr. Jenna Dixon
Hacking systemic lupus erythematosus (SLE): In May 2019 we hosted the Waterlupus health hackathon in Waterloo, ON. Waterlupus engaged stakeholders (advocacy organizations, patients, policy makers) to develop non-pharmacological interventions to improve the economic lives of SLE patients, increase public understanding of SLE, and establish partnerships between stakeholders. Funding source: Lupus Canada
We are now conducting a study assessing how SLE patients access health information pre and during COVID-19, to inform future delivery of accessible health information, minimize risk of illness and meet patient needs.
Outcomes of the Waterlupus hackathon, published July 2020 in Health Promotion and Chronic Disease Prevention in Canada, outlines the results of the Waterlupus health hackathon. Summary and further information on our hackathon: https://uwaterloo.ca/geographies-of-health-in-place/events/lupus-hackathon
Our current study is an online survey of Canadian and international SLE patients that will assess access to information. In-depth interviews with patients, physicians, and advocacy associations will help more fully understand the types of information sources patients trust, and how they share/use information to manage their disease. Data collection for this study is ongoing and will enable us to understand how and why SLE patients navigate health information during a public health crisis, and more aptly serve this community now and in the future.
Phenotyping SLE based on disease course: remitting-relapsing, persistently active and monophasic
Principal: Dr. Murray Urowitz
Team members: Dr. Dafna Gladman, Dr. Zahi Touma, Dr. Konstantinos Tselios, Dr. Jiandong Su
A major goal of clinical research in lupus is to improve disease management based on disease course. The significance and novelty of this research project lies in the opportunity to advance individualized care by precisely characterizing disease course. Patient identification and stratification early in the disease course will allow for targeted (or adjusted) therapies to prevent and/or reduce future lupus or drug-related complications.
The hypothesis of this research study was to test the clinical impression of the disease courses by modeling the course of the disease over time. Using our long term observational cohort we assessed the prevalence and characteristics of different patterns of disease course in the first 10 years after diagnosis of SLE.
Three patterns of disease course were found: Prolonged Remission (PR), Relapsing-Remitting (RR), Persistently Active (PA).
At 10 years, PA patients had more damage than the PR and RR patients. Black race and higher disease activity over the first 2 years were associated with a more severe disease course. RR and PA patients had an increased flare rate and accrued more osteoporosis, osteonecrosis and cardiovascular events.
In conclusion, the disease course pattern in SLE was primarily relapsing-remitting, while prolonged remission and persistently active disease were each observed in approximately 10% of the patients. Another 13% of the patients did not follow any of these “classic” patterns but achieved a solitary remission period of varying duration. The pattern of disease course and the time spent in remission were strongly related to damage accrual over 10 years as well as osteoporosis, osteonecrosis and atherosclerotic cardiovascular events over time.
This project was funded by a Lupus Canada Catalyst Grant and the Canadian Institutes of Health Research.
Immune and inflammatory mechanisms critical to the development of SLE, with a focus on RIPK3-dependent pathways
Principal: Dr. Joyce Rauch
Team members: Céleste Pilon, Elena Lonina, Dr. Jerrold S. Levine, Dr. Maziar Divangahi, Dr. Ciriaco Piccirillo, Dr. Jose A. Correa, Dr. Suman Setty, Dr. Marvin Fritzler and Dr. Christian Pineau
Our findings will provide proof of concept that targeting RIPK3 (Receptor-Interacting Protein Kinase 3)-dependent pathways in murine SLE results in prevention or improvement of this chronic and debilitating disease. These data could lead to Phase I trials of new therapeutic agents targeting RIPK3-dependent mechanisms in patients with SLE, which would impact both knowledge and patient care, and lead to improved treatments in SLE.
RIPK3 (Receptor-Interacting Protein Kinase 3) is a master regulator of cell death and inflammation. We have shown that deletion of RIPK3 prevents the development of SLE in an induced murine model. We hypothesize that RIPK3-dependent pathways are critical to the development of SLE, and that therapeutically targeting RIPK3 will prevent or ameliorate SLE.
We have published the following paper (Salem et al., lmmunol. Cell. Biol., 2019) related to this project demonstrating the following novel findings:
- β2-glycoprotein I (β2GPI), the self-antigen that induces our model of SLE, binds to cells dying by a RIPK3-dependent process (“necroptosis”).
- Necroptosis promotes activation of T cells reactive with β2GPI that help in the production of SLE autoantibodies.
- Targeting RIPK3 (by depletion in mice) results in reduced autoantibody production and kidney disease in a murine model of SLE.
These and future findings will provide proof of concept that inhibition of RIPK3-dependent pathways can diminish and/or prevent the development of murine SLE. This research will spur the development of novel diagnostic and therapeutic approaches in SLE, impacting both knowledge and patient care.
Current funding: CIHR Project Grant (PJT-159652)