Monash Researcher Awarded Grant to Study Tolerogenic Dendritic Cells

The Vasculitis Foundation awarded its “Dr. Chris Cox-Marinelli Young Investigator Award” — a one-year research grant totaling $49,822 — to Dragana Odobasic, PhD, a research fellow at Monash University in Melbourne, Australia.

The award is for Odobasic”s research on a subset of specialized immune cells, called tolerogenic dendritic cells, that can turn off the autoimmunity to myeloperoxidase (MPO) that causes some ANCA-associated vasculitis (AAV) cases, while leaving the remaining immune system unharmed.

Her findings were described in the study, “Tolerogenic Dendritic Cells for Antigen-Specific Immunosuppression in MPO-ANCA Vasculitis,” published in the Journal of the American Society of Nephrology.

ANCA-associated vasculitis is an autoimmune disease caused by the production of anti-neutrophil cytoplasmic autoantibodies (ANCA) that wrongly target and attack healthy immune cells called neutrophils, causing blood vessel inflammation and swelling in different tissues and organs.

MPO-AAV is one of the main forms of the disease, in which autoantibodies targeting the MPO protein in neutrophils cause damage to small blood vessels in the kidneys, resulting in kidney disease.

Conventional therapies for MPO-AAV are the administration of high doses of medications that suppress the immune system and reduce overall inflammation, such as corticosteroids and cyclophosphamide.

However, because these medications shut down the entire immune system instead of only blocking autoimmunity, patients often become more vulnerable to infections and certain types of cancer.

In her study, using a mouse model of MPO-AAV, Odobasic found that tolerogenic dendritic cells can effectively turn off the part of the immune system triggering autoimmune responses to MPO, while leaving the rest of the immune defenses intact.

If confirmed in a new study, these findings may propel the development of new therapies for MPO-AAV based on these specialized immune cells.

“The main focus of our research is to find effective, but safer therapies for vasculitis patients, with minimal side effects. Ideally, we’d like to turn off only autoimmunity to MPO, which is associated with vasculitis, without affecting the rest of the immune system. This would stop or reverse kidney damage caused by vasculitis, with negligible adverse effects,” Odobasic said in a press release.

With the new grant, Odobasic and colleague Stephen Holdsworth, MD, PhD, will continue to investigate the therapeutic potential of tolerogenic dendritic cells over the next year, using a well-established animal model of MPO-AAV and patient samples.

“This model closely resembles human disease,” Odobasic said. “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,” she said.

The grant awarded by the foundation to Odobasic bears the name of Christine Cox-Marinelli, MD, who was a strong advocate for vasculitis research, and a patient herself.

“Dr. Chris Cox-Marinelli was a friend, colleague, and tireless advocate for vasculitis research,” said Peter Grayson, MD, head of the Vasculitis Translational Research Program, and associate director of the National Institute of Arthritis and Musculoskeletal and Skin Diseases Fellowship Program.

“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,” Grayson said.