Researchers trace antibodies behind severe viral infections
Some people carry antibodies that block the body's early defenses against viruses, increasing their risk of developing severe illnesses such as severe COVID-19. Researchers at Karolinska Institutet have now identified the immune cells that produce these antibodies. The findings are published in the Journal of Experimental Medicine.
When viruses infect the body, an important defense system is activated that relies on signaling proteins called interferons. In some individuals, however, antibodies are produced that block these signals, making it more difficult for the body to fight off infection. Such antibodies have previously been linked to severe COVID-19 and other serious viral infections.
In the new study, the researchers analyzed blood samples from patients with severe COVID-19 and from individuals with the rare disease APS-1. They were able to identify the B cells that produce the harmful antibodies and track how these cells develop.
“We have gained a clearer picture of where these antibodies come from. This may help us understand why some people are particularly vulnerable to severe viral infections. Our hope is that this knowledge will eventually contribute to improved diagnostics and new treatments,” says Qiang Pan-Hammarström, professor at the Department of Medical Biochemistry and Biophysics at Karolinska Institutet.
The researchers also found differences between the disease groups. In patients with severe COVID-19, the neutralizing antibodies primarily originated from memory B cells. In APS-1 patients, they were mainly found in so-called atypical B cells, which are often associated with long-term immune activation.
The study was conducted in collaboration with researchers from Uppsala University, Peking University, the Institute for Research in Biomedicine at Università della Svizzera italiana, and Karolinska University Hospital, as well as research institutions in Italy. The Knut and Alice Wallenberg Foundation, the Swedish Research Council, the EU's Horizon 2020 programme, and Nordstjernan funded the research, among others.
The researchers state that they may seek patents for the use of antibodies against type I interferons in diagnostics and treatment.
Publication
"Cellular origin and characterization of autoantibodies against type I IFNs in COVID-19 and APS-1", Rui Sun, Siyu Lin, Luca Simonelli, Benedikt Strunz, Anish Behere, Mattia Pedotti, Tian Xu, Fanglei Zuo, Likun Du, Hui Wan, Sara Lestani, Leire de Campos-Mata, Stelios Vlachiotis, Dorottya Kalmár, Karolinska KI/K COVID-19 Study Group, Kristoffer Strålin, Soo Aleman, Hans-Gustaf Ljunggren, Antonio Piralla, Fausto Baldanti, Olle Kämpe, Sophie Bensing, Lennart Hammarström, Nils Landegren, Zexian Zeng, Niklas K. Björkström, Luca Varani, Harold Marcotte, Qiang Pan-Hammarström. Journal of Experimental Medicine, online 3 November 2026, doi: 10.1084/jem.20260268.