A rare but deadly disease of the circulatory system is not one but two diseases with different causes hiding under one umbrella say scientists investigating ANCA-associated vasculitis.
A genome-wide association study of 1,233 UK patients and 5,884 controls – replicated in 1,545 Northern European patients, and 1,666 controls – revealed four genetic variants play a crucial role in causing ANCA-associated vasculitis, a condition in which blood vessels are attacked by the body’s own white blood cells.
The genes each play a role in the body’s natural response to injury and infection, but mistakes make the immune system turn against the body’s own blood vessels.
Furthermore, researchers from the University of Cambridge and European Vasculitis Genetics Consortium showed patients with the disease fell into two distinct genetic groups depending on which variants they had. In each case, the body produced a different antibody – a discovery which could lead to better ways of treating and diagnosing these two different auto-immune diseases.
“Our study demonstrates for the first time that ANCA-associated vasculitis is not really one condition, but two diseases with different causes hiding under one umbrella,” said Professor Ken Smith, Professor of Medicine at Cambridge.
“Because the condition is rare this has been difficult to prove until now. Our key finding is that an important difference between the two groups is in the genes, and not only in the symptoms we can see.”
A simple blood test can determine which group a patient belongs to, and Smith hopes the discovery will lead to new treatments to target each group.
“ANCA-associated vasculitis is one of several rare diseases affecting the circulation. Although well known to doctors, the genetic cause was unclear until now,” said Dr Hélène Wilson, Research Advisor at the British Heart Foundation, who funded the research.
“Current treatments that suppress the immune system do work, but they are not ideal and can cause problems. By shedding new light on this devastating, often fatal disease, this breakthrough could point towards new strategies for managing the condition in the future.”