CALOR: Cooling Autoinflammation with cLinically Oriented Research

MSFHR/Cassie and Friends Society for Children with Juvenile Arthritis and Other Rheumatic Diseases Scholar Award

Childhood rheumatic diseases such as juvenile arthritis, lupus, vasculitis and fever syndromes are the most common childhood chronic illnesses. In Canada, the diseases affect approximately 10,000 children and youth. The affected children have recurrent attacks of inflammation in joints, muscles, and critical organs due to inappropriate activation of blood cells and molecules in the immune system.  Some rheumatic diseases are life- or organ-threatening and all have significant potential for lifelong poor health and disability. There are no cures and few treatments that are specific and safe for a growing child.

This project, CALOR (Cooling Auto-inflammation with CLinically Oriented Research), aims to develop ways to better measure inflammation in these diseases, especially low levels of inflammation that, if present, may justify continuation or re-starting of therapy to stave off an inflammatory attack. The project uses advanced informatics and a systems biology approach, including novel cellular phenotyping of first responder cells of the innate immune system, to find markers of inflammation.

Project outcomes may include sensitive measures of subclinical inflammation that better direct treatment decisions for children with a rheumatic disease. Central to the approach is early engagement of clinicians and patients to establish research priorities, to connect affected families with each other, and ultimately to identify ways to support BC family doctors so that ongoing patient care can be close to home. The CALOR project is founded on a recently developed Canadian Auto-inflammation Disease Registry and a nucleus of invested clinicians, researchers and families at BC’s Children’s Hospital.

End of Award Update: September 2022

Most exciting outputs

The major goal of our research program is to improve the lives of children with rare diseases that cause inflammation in the bones, muscles and joints. Vasculitis is one of these diseases caused by inflammation in the blood vessels of major organs. This is a very rare disease in children, affecting approximately 1 in 250,000 children. One of the exciting things that we have been able to do is create the largest database of clinical information (from over 600 affected kids) and frozen samples (from over 250 affected kids) that allows us to do meaningful studies on this disease. Before this, studies described no more than 25 children with vasculitis. Even more exciting, we were able to identify nine children that were originally diagnosed with vasculitis but had a newly discovered (as of 2014) disease, called DADA2. This is important because the treatment for vasculitis and for DADA2 is different.

Impacts so far

The Michael Smith Health Research BC/ Cassie and Friends Society Scholar Award has given us the opportunity to develop a connection with Cassie + Friends Society, a national organization dedicated to advancing research, information, connection and support for children living with a rheumatic disease. This relationship has helped shape our research program (are we asking research questions that are meaningful to patients and families?) and educated our trainees about the challenges for families and patients in everyday life and as part of a research study. In the lab, we have established two tests to help physicians diagnose two rare childhood syndromes, called DADA2 and ‘Type I Interferonopathy (Type 1 IFN). Kids with these diseases benefit from particular biologic therapy, therefore, it is important that they get diagnosed and started on the correct treatment as soon as possible. In the first two years that we offered these tests, we were consulted up to three times monthly and proceeded with testing for 20 children from around the province who were referred to various subspecialties at British Columbia Children’s Hospital. Results of our testing was conclusive in all but one case, affirming the suspected disease in five cases, and supporting a change in treatment for six patients.

Potential future influence

Since 2015, we have had 42 aspiring researchers, from high school students through to postdoctoral fellows, contribute to our program of research. For the vast majority, this was their first exposure to patient-oriented research in a health care setting, and in the study of rheumatic diseases that affect children. Our alumni have pursued a variety of academic and health related careers, and we trust that in those pursuits they will share their knowledge and experience with others in order to generate continued support and enthusiasm for patient-centric studies, especially rare diseases that affect children.

 

Next steps

The Michael Smith Health Research BC/ Cassie and Friends Society Scholar Award has allowed us to build a solid foundation of infrastructure, resources, and key collaborations with Cassie + Friends Society and the Rheumatology Health Care Team at BC Children’s Hospital. We have secured new funding from the Canadian Institutes of Health Research and the (US) National Institutes of Health to continue to advance our understanding of rheumatic diseases in a way that will improve the lives of affected children.

 

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