Monash University, Department of Medicine, Melbourne, Australia
Study Title: “Tolerogenic Dendritic Cells for Antigen-Specific Immunosuppression in MPO-ANCA Vasculitis”
Investigator: Dragana Odobasic, PhD
Co-investigator: Stephen Holdsworth, MD, PhD, Professor, Monash University, Department of Medicine; Head, Clinical Immunology, Monash Health, Clayton, Victoria, Australia
Institution: Monash University, Department of Medicine, Centre for Inflammatory Diseases, Monash Health, Clayton, Victoria, Australia
Award: $49,822
Dragana Odobasic, PhD, a research fellow at Monash University in Melbourne, Australia, was awarded the Vasculitis Foundation’s (VF) “Dr. Chris Cox-Marinelli Young Investigator Award” in May for her study, Tolerogenic Dendritic Cells for Antigen-Specific Immunosuppression in MPO-ANCA Vasculitis. The award, a one-year grant totaling $49,822, was created in memory of Chris Cox-Marinelli, MD, a strong advocate for promoting the development of junior investigators toward a career in vasculitis.
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of autoimmune diseases (granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, and microscopic polyangiitis) that causes blood vessels to swell. One of the most common forms of AAV is caused by autoimmunity to myeloperoxidase (MPO), which mainly affects capillaries that filter plasma in the kidney. Autoimmunity is when the body’s immune system attacks its own cells, tissues, or organs.
Standard treatments for MPO-AAV involve high doses of drugs such as corticosteroids and cyclophosphamide. These drugs work by suppressing the entire immune system, not just autoimmunity to MPO. Unfortunately, this can leave patients highly vulnerable to serious, life-threatening infections and cancer, and can cause cardiovascular problems as well. Tolerogenic dendritic cells are specialized immune cells that can turn off autoimmunity only to MPO without affecting the rest of the immune system.
Dr. Odobasic and co-investigator, Stephen Holdsworth, MD, PhD, hope to show that these specialized immune cells could provide an ideal therapy for patients with MPO-AAV.
“The main focus of our research is to find effective, but safer therapies for vasculitis patients, with minimal side effects,” Dr. Odobasic explained. “Ideally, we would like to turn off only autoimmunity to MPO, which causes vasculitis, without affecting the rest of the immune system. This would stop or reverse kidney damage caused by vasculitis, with negligible adverse effects.”
Over the course of the next year, Dr. Odobasic and Dr. Holdsworth will be using an animal model of MPO-AAV vasculitis, which they uniquely established several years ago. “This model closely resembles human disease,” said Dr. Odobasic. “We will also collect blood cells from vasculitis patients to show that their own tolerogenic dendritic cells, made by treatment with an anti-inflammatory protein called interleukin-10, can turn off their autoimmunity to MPO.”
“This potential therapy is very important to vasculitis patients because it could be a new, effective and much safer treatment than what’s available at this time,” Dr. Odobasic added. “It could improve patients’ quality of life by reducing complications and treatment side effects, which are currently experienced with the standard therapies.”
Dr. Cox-Marinelli, for whom the award was created, began her career in neurosurgery at the University of Minnesota, but was diagnosed with vasculitis in 2001, ending her work as a surgeon. Dr. Cox-Marinelli held different roles with the VF, including membership in the Board of Directors.
VF Research Committee member Peter Grayson, MD, who is head of the Vasculitis Translational Research Program, and Associate Director of the National Institute of Arthritis and Musculoskeletal and Skin Diseases Fellowship Program, expressed excitement about the award.
“Dr. Chris Cox-Marinelli was a friend, colleague, and tireless advocate for vasculitis research,” he said. “I am thrilled to see the VF Young Investigator’s Award in memory of Dr. Cox-Marinelli be given to Dr. Dragana Odobasic, whose exciting research proposal seeks to train the immune system to protect itself against factors that contribute to inflammation in ANCA-associated vasculitis.”
Kathy Marinelli and her family said it is a great comfort to see Dr. Cox-Marinelli’s passion continue through the future work of Dr. Odobasic. “Dr. Christine Cox-Marinelli was passionate about furthering research in vasculitis, an illness that she struggled with for over 17 years. She would be thrilled to be supporting the VF Young Investigator’s Award in vasculitis research.”
