In February, the VF Board of Directors approved three new research studies for funding, bringing to a total, $2,109,847,10, the VF has committed to supporting vasculitis research since 2002. The VF Research Program, established in 2002, is funded through the generous donations of our members and extended vasculitis community. The VF has 14 studies already underway in the United States, Australia, Austria, Canada, Germany, Italy, and the United Kingdom, with an additional 25 studies completed.
The three studies, selected from a field of 28 applications, represent new areas of research for the VF, including a study of autoantibodies that cause inflammation, a trial on chronic, recurrent skin vasculitis, and a study on a novel urine biomarker for treatment of glomerulonephritis.
Investigator: Prof. dr. Peter Heeringa
Institution: Department of Pathology and Medical Biology, Vasculitis Expertise Center, University Medical Center, Groningen, Netherlands
Title: Analysis of glycosylation of Proteinase 3-ANCA IgG variable domains
Award: $49,500, one-year
ANCA associated vasculitides (AAV) are severe diseases that result from attack by one’s own immune system (autoimmune disease). This is caused by circulating proteins (autoantibodies) produced by cells from the immune system that target and activate white blood cells causing inflammation in small blood vessels throughout the body.
The research proposed in this project will study the autoantibodies that cause the inflammation. Antibody proteins are coated with sugars, the extent and composition of which determines their
function. In this project we hypothesize that the autoantibodies in AAV differ from “normal” antibodies with respect to the amount of sugar groups attached and therefore impacts their function. To this end, we will isolate the autoantibodies from patient’s blood and characterize in detail the extent and composition of the sugar coating. We expect this research will inform efforts to refine laboratory tests for AAV diagnosis and patient monitoring and, in the future, reveal whether interfering with the sugar coating of autoantibodies can be used for therapeutic applications.
Investigator: Professor Mark Little
Institution: Trinity Health Kidney Centre, Nephrology, Renal Inflammation Group, St. James Hospital, Dublin, Ireland
Title: Rational treatment of glomerulonephritis using a novel urine biomarker
Award: $49,294, one-year
This project is focused on development of a new biomarker test in the diagnosis and monitoring of crescentic glomerulonephritis (CGN), a severe form of inflammatory kidney injury. This test relies upon identification of a single protein in the urine: soluble CD163. This is shed from activated white blood cells within the kidney, which are in direct ommunication with the urine. We have discovered that the level rises when kidney vasculitis is active, and is not elevated in other causes of kidney disease. Therefore, it is highly specific for CGN.
We aim to track urinary sCD163 during the first few months of treatment for CGN to investigate its usefulness as a biomarker to help us decide when to switch to less intensive maintenance treatment. This will be achieved by engagement with three clinical research facilities in the Dublin area and the recruitment of 40 patients, who will be sampled 7-12 times over the year following commencement of therapy.
Most current biomarker programmes rely upon panels of compounds. We have discovered a single protein that closely mirrors CGN, which has the potential to provide a guide for clinicians as to when to discontinue potentially toxic induction therapy. The current project will bring this closer to a point of care test that will improve the care of patients with vasculitic disorders.
Investigator: Robert Micheletti, MD, Assistant Professor
Institution: Dermatology and Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
Title: A randomized multicenter study for isolated skin vasculitis (ARAMIS)
Award: $50,479, one-year
Vasculitis is a rare disease that damages blood vessels. When it affects the skin, it causes multiple burning or itchy purple spots which can become painful ulcers or become infected. For patients who get such lesions recurrently, vasculitis of the skin can be debilitating.
Unfortunately, we do not know what medications work best for this condition. There have not been any studies which address this question adequately. Therefore, doctors often try various medications at different doses before hitting on an effective regimen.
ARAMIS is a trial specifically for chronic, recurrent skin vasculitis which will test three medications—dapsone, colchicine, and azathioprine—used commonly but never proven to work for that condition. Patients will receive one of the three medications titrated to a goal dose and duration designed to evaluate its effectiveness. If the medication does not help after 3-6 months, patients will be switched to one of the other two medications, and the process will be repeated. The primary end point will be significant improvement or complete resolution of skin vasculitis after six (6) months on a particular medication.
The results from these two study stages will be combined to determine which medication is best at decreasing skin lesions and improving patient symptoms. If the study is successful, doctors will for the first time have high-quality scientific evidence to guide how they treat skin vasculitis.
Because skin vasculitis is uncommon and understudied, it truly represents an area of unmet need. With the administrative support of the Vasculitis Clinical Research Consortium (VCRC), we have assembled a multicenter, interdisciplinary team of collaborating rheumatologists and dermatologists to help answer this question, without whom this work would not be possible.