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Scientists at the Garvan Institute of Medical Research have uncovered a groundbreaking mechanism through which chronic hepatitis C infection leads to autoimmune disease, challenging long-standing beliefs and paving the way for novel treatment strategies.
Chronic hepatitis C virus (HCV) infection, which affects approximately 58 million people globally, is known for its ability to trigger severe autoimmune diseases in some patients. One such condition is cryoglobulinemic vasculitis, which occurs in up to 15% of HCV cases. This disorder involves the formation of antibodies that attack blood vessels, potentially causing damage to multiple organs throughout the body.
Historically, researchers believed that this autoimmune response was triggered by molecular mimicry—where viral proteins resembled the body’s own proteins, leading the immune system to mistakenly target both. However, a groundbreaking study by the Garvan Institute’s research team has disproven this theory, offering a new perspective on how infections can cause autoimmune diseases.
New Discovery: Rogue B Cell Mutations
The study, published in the journal Immunity, reveals that the key to understanding this autoimmune response lies not in viral proteins but in mutations of “rogue clone” B cells. These B cells produce harmful autoantibodies, which attack the body’s tissues and blood vessels, ultimately leading to cryoglobulinemic vasculitis.
Professor Chris Goodnow, Head of the Immunogenomics Lab at Garvan and co-senior author of the study, emphasized that the discovery shifts our understanding of how infections can trigger autoimmune diseases. “By pinpointing these rogue clones, we can better understand how to target them, potentially revolutionizing treatment approaches for autoimmune diseases.”
A ‘Perfect Storm’ of Mutations
To unravel this phenomenon, the research team used cutting-edge single-cell analysis and whole genome sequencing to study the immune cells of four patients with HCV-induced cryoglobulinemic vasculitis. They identified specific rogue clone B cells that were present in unusually high numbers and producing autoantibodies responsible for the autoimmune response.
Lead author Dr. Clara Young explained, “The prevailing theory was that B cells trained to recognize the foreign virus became confused and attacked the body. Our findings, however, show that during chronic hepatitis C infection, viral particles trigger persistent mutations in B cells, leading to the formation of rogue clones.”
Dr. Dan Suan, co-senior author and Clinical Director of the Hope Research Program at Garvan, added, “Our research identifies three types of genetic mutations necessary for the development of this autoimmune disease. Two of these mutations are a normal part of B cell development, but the presence of chronic viral infection creates a persistent stimulus. The third mutation, which is linked to blood cancers, occurs randomly over time. This combination of mutations creates the conditions for the disease.”
Implications for Treatment and Prevention
The team’s findings offer hope for developing targeted therapies to prevent autoimmune complications in patients with chronic viral infections. Professor Goodnow stated, “Understanding this underlying mechanism opens new avenues for predicting and preventing autoimmune responses. We can focus on stopping the formation of these autoantibodies before they trigger harmful reactions in the body.”
Dr. Young also highlighted the broader relevance of the study, stating that the insights could inform the understanding of other infection-associated autoimmune conditions, such as Guillain-Barré syndrome and multiple sclerosis, which are linked to bacterial and viral infections.
“This is a significant step forward in our efforts to tackle the root causes of autoimmune diseases,” added Dr. Suan. “Rather than merely managing symptoms, we now have the potential to target the mutations that drive autoimmunity.”
The team’s discovery provides a new framework for studying autoimmune disease and could significantly alter the approach to treating these complex and often debilitating conditions.
Reference: A triad of somatic mutagenesis converges in self-reactive B cells to cause a virus-induced autoimmune disease, Immunity (2025). DOI: 10.1016/j.immuni.2024.12.011. www.cell.com/immunity/fulltext
