The studies are:
1. Endothelial Cell Inflammasomes in ANCA-Associated Vasculitis
Investigator: Dan Jane-Wit, MD, PhD
Co-investigator: Caodi Fang, MS
Institution: Yale University
Award: One-year, $50,000
Inflammasomes are shown to play a role in a number of other diseases associated with inflammation including gout, Muckle-Wells Syndrome, Familial Cold Autoinflammatory Syndrome and many others.
The research focuses on the role of inflammasomes in the development of atherosclerosis in ANCA associated vasculitis.
The implications from this research could include a better understanding of why patients with ANCA-associated vasculitis develop atherosclerosis. The findings could then be used to develop strategies to prevent atherosclerosis and cardiovascular diseases.
2. Metabolic Dysregulation of Pro-inflammatory Responses in DADA2 Vasculitis
Investigator: Sonia Sharma, PhD
Co-investigators: Rekha Dhanwani, PhD; Mohit Jain, MD, PhD
Institution: La Jolla Institute for Allergy and Immunology
Award: One-year, $50,000
Adenosine deaminase 2 deficiency (DADA2) is an inherited disorder which can cause vasculitis of medium-sized blood vessels. The disease is caused by mutations in the CECR1 gene. DADA2 was first discovered in 2014. DADA2 can present similarly to polyarteritis nodosa.
It is not clear how DADA2 leads to vasculitis and there are currently limited treatment options. Dr. Sharma and colleagues have found that a deficiency of adenosine deaminase 2 can cause the accumulation of purines. The over-accumulation of purines can lead to an over-exaggerated inflammatory response.
The research aims to determine the ways in which an accumulation of purines affects the immune system. This is the first research to explore the metabolic basis for the disease. The implications of this research could include the development of new treatment strategies for DADA2.
3. Long-Term Patient Follow-up of ANCA-Associated Vasculitis
Research team: David Jayne, FMedSci, Laura Moi, M.D., Ingeborg Bajema, M.D., Thomas Hauser, M.D., Alfred Mahr, M.D., MPH, Ph.D., Kerstin Westman, M.D., Peter Hoglund, M.D., Mikkel Fauschou, M.D. and Raashid Luqmani DM FRCP, FRCP(E)
Institution: University of Cambridge, United Kingdom
Award: One-year, $62,000
There is limited data regarding long-term outcomes in forms of ANCA-associated vasculitis and factors that prevent adverse outcomes.
These researchers are developing a large database using the information collected as part of ANCA trials from 1995 to 2010. The team is examining factors such as survival, long term kidney function, co-morbidities, relapse status, vasculitis-related damage, drug exposure, mortality, cancer rates, cardiovascular events, drug safety, relapse rate and other kidney-related outcomes.
Dr. Moi, the fellow supported by the grant, will manage the project.