Type I interferon autoantibody footprints reveal neutralizing mechanisms and allow inhibitory decoy design
In a recent study led by Kevin Groen and senior author Benjamin G. Hale, researchers uncovered how certain harmful autoantibodies can disrupt the body’s natural antiviral defenses—and proposed an innovative strategy to neutralize them. Published in the Journal of Experimental Medicine, this work provides valuable insight into why some individuals develop severe viral illnesses, including COVID-19.
Our immune system uses proteins called type I interferons (IFNs) to detect and control viral infections. However, in some people—particularly older adults or those with chronic conditions—autoantibodies form that target and neutralize these IFNs, leaving the body more vulnerable. These harmful autoantibodies have been linked to severe outcomes in COVID-19, influenza, and other infections.
To investigate how these autoantibodies work, Groen and colleagues studied blood samples from individuals with severe COVID-19 and from older adults living with HIV who participate in the SHCS. The SHCS was crucial for this research because it provided access to a well-characterized population with longitudinal data, allowing the team to analyze how IFN-targeting autoantibodies develop and persist over time in aging individuals. Without the SHCS’s detailed and curated clinical data, such insights would not have been possible.
The team discovered that the autoantibodies consistently target specific regions—or “footprints”—on IFN molecules that are essential for triggering an immune response. To counter this, they engineered “decoy” interferons—modified versions that attract and bind the autoantibodies without affecting real IFN function. These decoys successfully prevented IFN neutralization and selectively removed the harmful antibodies from plasma.
This scientifically rigorous and creative study—driven by the Hale lab—offers both a clearer understanding of immune dysfunction in viral disease and a promising therapeutic strategy. It also highlights the critical role of large, collaborative studies like the SHCS in enabling cutting-edge biomedical research.