IgA, liver immune cells interact to amplify inflammation

Findings point to new treatment strategies, biomarker candidates

From left: Seong Pil-soo, a professor in the Division of Gastroenterology and Hepatology at Seoul St. Mary's Hospital; Tak Kwon-yong, a clinical instructor in the same division; and Kim Min-gu, a master's student at the Catholic University of Korea. [Seoul St. Mary's Hospital]
From left: Seong Pil-soo, a professor in the Division of Gastroenterology and Hepatology at Seoul St. Mary's Hospital; Tak Kwon-yong, a clinical instructor in the same division; and Kim Min-gu, a master's student at the Catholic University of Korea. [Seoul St. Mary's Hospital]

A new study has found that immunoglobulin A (IgA), an antibody that protects the gut lining, may play a role in driving liver inflammation and hepatocyte damage in alcohol-associated liver disease.

A research team led by Professor Seong Pil-soo of the Division of Gastroenterology and Hepatology at Seoul St. Mary's Hospital, Catholic University of Korea, said Monday it had identified what it calls a "gut-liver IgA immune axis" — a pathway through which elevated IgA in alcohol-associated liver disease interacts with liver immune cells to trigger inflammatory responses and hepatocyte damage. Clinical instructor Tak Kwon-yong and Kim Min-gu, a master's student in the Department of Medical Science at Catholic University of Korea, served as co-first authors.

IgA is a defense antibody found in mucous membranes lining surfaces exposed to the external environment, such as the gut and respiratory tract, where it blocks bacteria and viruses. In the gut, it plays a key role in mucosal immunity by preventing intestinal microbes from entering the body.

Elevated blood IgA levels in patients with alcohol-associated liver disease had been documented previously. What remained unclear was why IgA levels rise and whether the increase is merely a consequence of the disease or whether elevated IgA actively contributes to liver inflammation and damage.

The research team combined analysis of patient blood and liver tissue with animal models, spatial transcriptomics and human immune cell experiments. The researchers focused on monocytes and macrophages — cells that help clear foreign substances and repair tissue but can trigger inflammation when overactivated.

Patient analysis showed that higher blood IgA levels corresponded to greater IgA accumulation in liver tissue, and IgA was found bound to monocytes and macrophages in the liver. The pattern of IgA binding to immune cells was also associated with increased levels of interleukin-1 beta (IL-1β), a cytokine involved in inflammatory responses.

The findings suggest that elevated IgA in alcohol-associated liver disease is more than a blood test marker — it may actively participate in the inflammatory responses of liver immune cells.

Animal models administered alcohol showed concurrent increases in blood IgA, IgA binding to liver macrophages, IL-1β expression and liver damage. When the animals were given FTY720, a drug that regulates immune cell migration, blood IgA levels fell, IgA-bound liver macrophages decreased, and both inflammatory responses and liver damage were reduced.

The team said that while previous gut-liver axis research had focused mainly on gut microbes or microbially derived substances, this study demonstrates that immune antibodies produced in the gut can themselves regulate liver inflammation.

"IgA is an antibody our body absolutely needs for protection, so simply suppressing it altogether cannot be the treatment goal," Professor Seong said. "What matters is finding a treatment strategy that selectively targets only the pathological gut-liver IgA immune axis while preserving normal immune function."

The team plans to validate blood IgA levels and hepatic IgA immune responses as biomarker candidates for alcohol-associated liver disease, and to investigate treatment strategies that selectively block the interaction between IgA and liver macrophages.

The findings were published in the international journal Gut.

Meanwhile, according to the Korea Disease Control and Prevention Agency's 2025 Community Health Survey, the monthly drinking rate among Korean adults exceeded 50 percent, reaching 57.1 percent. The high-risk drinking rate — defined as heavy drinking on two or more occasions per week — stood at 12.0 percent.


woo@heraldcorp.com