MIS-C, a rare post-COVID inflammatory syndrome in children, may occur when the immune system mistakenly identifies its own proteins as those of the virus.
Scientists have identified the trigger that causes inflammation to spiral out of control in some children following a COVID-19 infection.
It turns out that the immune system mistakenly recognizes a protein produced in various parts of the body as foreign because it resembles one found in SARS-CoV-2, the virus responsible for COVID-19.
The condition, known as multisystem inflammatory syndrome in children (MIS-C), was first identified early in the pandemic in a small fraction of children who had recovered from COVID-19.
Many of these children were initially asymptomatic during their viral infection but developed life-threatening, uncontrollable inflammation in the heart, brain, skin, blood, or digestive system two to six weeks later.
MIS-C always presents with a fever, but it can also lead to symptoms such as weakness, dizziness, stomach pain, or a rash.
Until recently, scientists were uncertain about the exact connection between COVID-19 and MIS-C, or why the immune system might attack the body after an infection. To investigate the causes of inflammation in MIS-C, researchers analyzed the immune systems of 199 children with MIS-C and 45 who recovered without developing the condition.
The study, published on August 7 in the journal Nature, identified 30 autoantibodies—antibodies that attack the body’s own tissues rather than foreign invaders—that were present in patients with MIS-C but absent in those without the condition.
The autoantibodies with the most pronounced profile targeted a protein named SNX8, which is present in nearly every part of the body due to its role in sorting and transporting molecules within cells.
It was discovered that a portion of the coronavirus’s “nucleocapsid protein” closely resembles the part of SNX8 that these autoantibodies target. The nucleocapsid protein, which forms part of the virus’s outer shell enclosing its genetic material, shares similarities with SNX8. This resemblance suggests that, in some patients, the immune system might be confusing SNX8 with its SARS-CoV-2 counterpart and consequently attacking tissues that contain SNX8.
To support this theory, the team examined T cells, which identify and destroy virus-infected cells, from patients with and without MIS-C. They found that only T cells from MIS-C patients responded to both SARS-CoV-2 and SNX8, reinforcing the mistaken-identity hypothesis. This finding could lead to new methods for diagnosing the condition in the future.
However, SNX8 is probably not the entire explanation for MIS-C.
Senior author Joseph DeRisi, a professor of biochemistry and biophysics at the University of California, San Francisco (UCSF), told Live Science, “We believe that multiple rare factors combine to lead to MIS-C. Antibodies are one component, but not the sole factor.”
Regardless, MIS-C is now much less of a concern than it used to be.
Dr. Aaron Bodansky, the study’s first author and a pediatric critical care fellow at UCSF, remarked, “What’s intriguing is that MIS-C has mostly disappeared, except in children who are unvaccinated or whose vaccine protection has diminished. Vaccinating helps predispose the immune system to SARS-CoV-2, reducing the time available for this unusual response to develop.”
However, decreasing vaccination rates for the new, updated COVID-19 vaccines could indicate potential problems. “I consider that a significant concern,” DeRisi said. “If this trend continues, I anticipate we might see an increase in MIS-C cases.”
For now, they plan to use their study as a model to explore other autoimmune or inflammatory conditions that might be triggered by viral infections, such as diabetes or multiple sclerosis.
