By IDSE News Staff
Scientists at the Garvan Institute of Medical Research have discovered how hepatitis C virus (HCV) can lead to cryoglobulinemic vasculitis in up to 15% of cases, disproving a long-standing theory.
Scientists believed this autoimmune response occurred because viral proteins mimicked the body’s own proteins, confusing the immune system into attacking both. Instead, the critical trigger may be mutations in “rogue clone” B cells (Immunity 2025 Jan 15. doi:10.1016/j.immuni.2024.12.011).
“This discovery fundamentally changes our understanding of how infections can cause autoimmune conditions,” said Chris Goodnow, BVSc, BSc(Vet), the head of the Immunogenomics Lab at Garvan, in Darlinghurst, Australia, and the study’s co-senior author. “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.”
Using sophisticated single-cell analysis techniques and whole-genome sequencing, the researchers analyzed immune cells in the blood of four patients with HCV-triggered cryoglobulinemic vasculitis. They identified the specific rogue clone B cells that were present in large numbers and produced harmful autoantibodies.
“The long-standing theory is that B cells trained to recognize the foreign virus become confused and target the body instead—a phenomenon referred to as molecular mimicry. What our study showed was that during a chronic hepatitis C infection, antibodies on the virus surface form an antibody cluster that persistently stimulates the B cells to mutate,” explained lead author Dr. Clara Young, a research officer at Garvan. “This continual mutation, we found, eventually leads to development of the rogue clones that cause cryoglobulinemic vasculitis.”
Three types of genetic mutations, two of which occur normally in B cells, are required for the autoimmune disease to develop, according to Dan Suan, PhD, the co-senior author and clinical director of the Hope Research Program at Garvan. “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,” he added.
“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,” Dr. Suan said.
This work was supported by the Bill and Patricia Ritchie Foundation, Croall Foundation, John Brown Cook Foundation, and Miss Lyn Unsworth.
