Research led by the Garvan Institute of Medical Research in Australia clarifies the connection between infection with the hepatitis C virus and the onset of cryoglobulinemic vasculitis, a serious autoimmune condition characterized by the build up of abnormal proteins and inflammation in the blood vessels.
Different viral infections have been proposed as triggers for a number of different autoimmune diseases, but the actual mechanism behind this process is not well understood.
The research, published in the journal Immunity, shows that B cell mutations in combination with the viral proteins trigger autoimmunity and subsequent cryoglobulinemic vasculitis in people infected with hepatitis C, rather than viral proteins copying the bodies own proteins and triggering the body to attack itself.
“This discovery fundamentally changes our understanding of how infections can cause autoimmune conditions,” said co-lead author Chris Goodnow, a professor and group leader at Garvan Institute of Medical Research, in a press statement.
“By pinpointing these rogue clones, we can better understand how to target them, which is a potentially transformative approach to treating autoimmune disease in patients.”
Hepatitis C impacts an estimated 58 million people around the world and 15% of these individuals also go onto develop cryoglobulinemic vasculitis. In this study, the research team used deep single-cell multiomic technology to analyze samples from four patients with hepatis C and cryoglobulinemic vasculitis to try and better characterize the pathway to autoimmunity in these people.
They found that patients with cryoglobulinemic vasculitis had pathogenic B cell clones with many mutations in them, even when the hepatitis C virus could no longer be detected. Some of these mutations were similar to those seen in blood cancers such as leukemia and lymphoma.
“Our research shows that three types of genetic mutations are required for the autoimmune disease to develop,” said Dan Suan, PhD, co-lead author and clinical director of the Hope Research Program at Garvan.
“Two of these mutations occur normally in B cells, but the presence of chronic viral particles that can’t be cleared creates ongoing stimulation. The third mutation, linked to the development of blood cancers, occurs by chance over time. This perfect storm of mutations allows the cells to accumulate in large enough numbers to cause the autoimmune disease.”
The researchers believe that this newly discovered mechanism may help predict and also prevent autoimmune diseases being triggered in the future and may also help develop more targeted treatments for conditions such as cryoglobulinemic vasculitis.
“Mutations occur in B cells as part of their normal development and understanding how they can drive autoimmunity is a significant step forward in our mission to eliminate the root cause of autoimmune disease rather than just managing symptoms,” said Suan.
