A new research review published in the Journal of Clinical Medicine outlines the evolving landscape of autoantibodies in primary biliary cholangitis (PBC).
The study’s authors analyzed decades of research on established and emerging serological markers, focusing on how they help diagnose PBC, what they may reveal about how the disease develops and their potential roles in personalized care for individuals with the condition.
For most people with PBC, the disease is diagnosed by the presence of anti-mitochondrial antibodies (AMAs), particularly the AMA-M2 subtype. These antibodies are found in about 90% to 95% of patients and can appear years before symptoms develop. They target specific proteins inside the mitochondria of bile duct cells, reinforcing the idea that PBC is driven by a highly targeted autoimmune response.
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However, not everyone with PBC tests positive for AMAs. For those individuals, PBC-specific antinuclear antibodies (ANAs) are especially important. Antibodies such as anti-gp210 and anti-sp100 are strongly associated with PBC and can help confirm a diagnosis when AMAs are absent. These antibodies are already used in clinical practice and are considered highly specific for the disease.
The authors also highlighted newly identified autoantibodies, including anti-KLHL12 and anti-RPL30. These emerging markers are drawing attention because they may help identify PBC in people who test negative for traditional antibodies. While they are not yet routinely used in clinics, they could eventually expand diagnostic options and improve confidence in difficult cases.
Additionally, the authors noted there has been a shift in science’s understanding of how autoantibodies arise in PBC. Instead of a simple loss of immune tolerance, evidence suggests that changes in bile duct cells (possibly triggered by bile acid injury) may alter mitochondrial proteins in a way that makes them appear foreign to the immune system. This process could spark the production of AMAs and ongoing inflammation.
The authors conclude that broader autoantibody testing and more detailed profiling could help better define PBC subtypes, improve early diagnosis and support a more personalized approach to care in the future.
“Autoantibody-based strategies — particularly the next generation of ANA profiling — hold promise as pivotal tools for advancing personalized medicine, enabling earlier intervention, and ultimately improving long-term outcomes for patients with PBC,” they concluded.
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