Multisystem inflammatory syndrome in children (MIS-C)—a rare, life-threatening condition linked to the virus that causes COVID-19—may result from an immune system attack on one of the body’s own proteins, suggests a study funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). The protein, SNX8 (Sorting Nexin 8) helps regulate a chemical pathway involved in the immune response against viruses. A section of SNX8 greatly resembles a protein fragment of SARS-CoV-2 that is hidden inside the virus and not typically the primary target of the immune system. By recognizing this usually hidden viral protein fragment, the immune system also learns to target SNX8, potentially leading to the inflammation of the brain, eyes, skin, and internal organs that characterizes the syndrome.
The study, by Aaron Bodansky, M.D., of the University of California, San Francisco, and colleagues, appears in the journal Nature.
Background
When children get SARS-CoV-2 infections, they usually develop mild symptoms, but some go on to develop MIS-C. In addition to widespread inflammation, many children with MIS-C develop antibodies to their own tissues and alterations in the activity of their immune cells. Although MIS-C may occur after SARS-CoV-2 infection, no previous studies have shown how the infection might cause MIS-C.
Results
For the current study, researchers enrolled 199 children who developed MIS-C after having SARS-CoV-2 infection and 45 children who had SARS-CoV-2 but did not develop MIS-C. They analyzed blood samples for both groups for signs of immune activity against all human proteins and against all proteins made by SARS-CoV-2.
They found that patients with MIS-C had antibodies that targeted a hidden segment of a SARS-CoV-2 protein and the human SNX8 protein. They showed that segments of these proteins were almost identical biochemically and that by learning to recognize this viral protein segment, the immune system also mistakenly targeted the SNX8 protein. Similarly, among the MIS-C patients, infection-fighting immune cells known as cytotoxic T cells also mistook SNX8 as the viral protein.
Significance
“It’s important to point out that COVID-19 vaccines target the spike protein, which is on the virus’s outer protein coat,” Dr. Bodansky said. “The protein we identified is in the nucleocapsid—deep inside the virus—and has nothing to do with the spike protein or with the vaccine.”
The authors believe their findings may shed light on other conditions in which an immune system attack on the body’s own tissues occurs after a viral infection, such as multiple sclerosis and type 1 diabetes.
Reference
Bodansky, A, et al. Molecular mimicry in multisystem inflammatory syndrome in children. Nature. 2024. https://doi.org/10.1038/s41586-024-07722-4
BACK TO TOP