The VF Board of Directors is pleased to announce that it has selected three new research studies for funding this year. The Vasculitis Foundation collaborates with researchers around the world to fund the most promising studies.
The goals of the Research Program are to fund high quality research improve the quality of life for patients with vasculitis and ultimately find the cause/s and cure for vasculitis.
The Vasculitis Foundation is funding a one-year study led by principal investigator, Jonathan Choy, Ph.D., from Simon Fraser University, Burnaby, British Columbia Canada.
The Vasculitis Foundation has funded a two-year study led by Susan Jick, Dsc, Professor of Epidemiology Director Boston Collaborative Drug Surveillance Program Boston University School of Public Health, Boston, Massachusetts. The VF provided the $ $98,641 award through its VF Research Program.
Vasculitis is an inflammation of blood vessels which is mistakenly thought to be an attack by the immune system. It can affect any of the body’s blood vessels and be fatal if left untreated. Most of the vasculitic syndromes respond well to steroid drugs, but vasculitis can still lead to organ damage or even death from its effect on blood vessels, flares (new symptoms develop), and treatment side effects. Thus, reducing the risk of undesired outcomes or death in patients living with vasculitis becomes an important treatment goal.
Jick says the project will use the UK-based Clinical Practice Research Datalink, which provides de-identified electronic health data for a large primary care population, to identify a vasculitis population (including patients with giant cell arteritis, granulomatosis with polyangiitis, and Polyarteritis nodosa) and a non-vasculitis population with similar age and sex distribution.
“This project will also estimate the rates of death at 1, 3, 5 and 10 years of follow-up after the first vasculitis diagnosis and compare them to the corresponding rates in the non-vasculitis population,” explains Jick. “An essential goal of this study will be identifying potential risk factors for death using a survival analysis. This study will improve our understanding of vasculitis-related health problems and lead to better treatment.”
Investigator: Renate Kain, MD, PhD
Institution: Medical University of Vienna, Vienna, Austria
Title of Application: Role of LAMP-2 in tolerance to ANCA antigens
Award: $50,000, one-year
Summary: Despite recent advances in treatment, ANCA-associated vasculitis (AAV) still causes serious morbidity especially after the acute injury has been controlled, emphasizing the need for better ways to monitor disease activity and personalize immunosuppressive therapy. It was thought that antibodies to the classical ANCA targets would be ideal biomarkers, myeloperoxidase (MPO) and proteinase-3 (PR3), because of the overwhelming evidence that they cause injury. Surprisingly, this is not the case and they correlate badly with disease activity, suggesting either that current assays don’t measure the damaging antibodies or that additional factors are required for injury. We identified autoantibodies to a protein called LAMP-2 as a potential missing link because they are found together with antibodies to MPO or PR3 in 80-90% of individuals with active AAV. Much of our research is designed to find out why these two types of autoantibody are found so commonly together in AAV.
LAMP-2 is located both in lysosomes inside the cell and on the cell surface and is important for presenting antigens to the T cells that initiate immune responses. We showed recently that LAMP-2 acts as a receptor on the surface of human antigen presenting cells that facilitates internalization of molecules and their targeting to the compartment where antigens are loaded onto the molecules that present them to T cells. We now propose to use novel techniques to fluorescently label LAMP-2 and so provide a unique opportunity to discover whether it also promotes uptake of MPO and PR3 by antigen presenting cells before transporting them into the antigen loading compartment; and also to determine whether anti-LAMP-2 antibodies interfere with the process. If we are correct, the results will identify the link between antibodies to LAMP-2 and to MPO and PR3 and lead on definitive studies to determine whether anti-LAMP-2 antibodies influence autoimmunity to them.