UNC awarded $5 million NIH grant to explore disease that inflames blood vessels

October 03, 2000

CHAPEL HILL - A groundbreaking $5 million federal grant to the University of North Carolina at Chapel Hill School of Medicine could help researchers find the cause of an often debilitating blood vessel inflammation of the kidneys, lungs, skin, heart, and other organs.

The grant from the National Institute of Diabetes and Digestive and Kidney Diseases will support a series of investigations into ANCA vasculitis, a disease encompassing several overlapping conditions of small blood vessel inflammation (including Wegener's granulomatosis).

"This grant will let us explore the cause of the disease so we can figure out a better treatment," said Ronald J. Falk, MD, professor of medicine at the university, nephrology division chief, and a pioneering vasculitis researcher.

Ten years ago, Falk and his Carolina colleague J. Charles Jennette, MD, professor of medicine and chair of pathology and laboratory medicine, were the first to suggest that specific antibodies found in patients with small vessel vasculitis were the disease triggers.

These are the two types of ANCA autoantibodies discovered about ten years ago, one by researchers in the Netherlands, the other by Falk and Jennette. ANCA means anti-neutrophil cytoplasmic antibodies.

In ANCA vasculitis, the body begins producing antibodies against specific components within neutrophils, which are leukocytes or white blood cells packed with potent infection-fighting granules. ANCA antibodies explode neutrophils, and when released, their granules help trigger inflammation.

"The disease is a 'kissing cousin' of another cause of vascular inflammation known as systemic lupus erythematosis, Falk said. "Each year, based on figures in the UK, ANKA vasculitis strikes an estimated six to ten people per million population. The UK figures apply to the United States, although ANCA vasculitis may, in fact, be more common here."

Why ANCA get produced, how they activate normal neutrophils to cause tissue damage, and exactly how the damage to small blood vessels occurs remain unclear.

"These are the big questions we'll explore," Falk said. "We also want to develop appropriate animal models for this human disease. We'll also study differences in the ability of patients' leukocytes when compared to normal individuals to do damage. And then there's a big question of whether certain environmental toxins cause the disease."

Falk points out that the research will involve molecular biology and cell biology studies of human blood - including antibodies and leukocytes - a series of animal model experiments, and detailed environmental exposure investigation.

"The disease may have a genetic component, an environmental component and probably an infectious disease component," he said

A member of the UNC Lineberger Comprehensive Cancer Center, the kidney specialist notes that therapy for the disease is about the same as it was 20 years ago. Patients may receive several medications, including steroids intravenously or in pill form. Other powerful and toxic drugs, such as prednisone and the cancer chemotherapies cyclophosphamide and methotrexate, carry a variety of side effects such as nausea, vomiting, bone marrow defects, and GI bleeding.

"Such treatment can be miserable. If we can't figure out the cause of the disease and what allows one to form antibodies, then we'll be stuck with these problematic therapies," Falk said.
media note:
Contact Dr. Falk

School of Medicine contact:
Les Lang

University of North Carolina Health Care

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