Autoantibody Increases the Risk of Inflammation, Blood Clots

Autoantibodies in COVID-19 patients found to contribute to the disease’s development. The novel coronavirus can release a flurry of overactive immune cells that produce toxic webs of proteins and DNA called neutrophil extracellular traps, or NETs.

Research team analyzed serum from over 300 hospitalized COVID patients, searching for a novel autoantibody that shields the toxic NETs from being destroyed and produces a lasting noxious effect in a patient’s body.

Findings published in JCI Insight reveal elevated levels of the anti-NET antibodies in many of the participants.

"We see a slew of different antibodies produced in COVID-19 patients, and now we discovered another clinically significant one that is likely contributing to severe COVID," said Yu (Ray) Zuo, M.D., lead author and a rheumatologist at Michigan Medicine.

"They feed into the inflammatory storm that we’re seeing in the most serious cases of viral infection."

Researchers found the serum from patients with higher levels of anti-NET antibodies can’t degrade the toxic traps. While a healthy person’s serum should completely disintegrate the extracellular traps, the purified anti-NET antibodies significantly hindered the process.

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"We knew that people with severe forms of COVID have higher amounts of these neutrophil extracellular traps, which amplify inflammation and promote blood clot formation," said Jason Knight, M.D., corresponding author of the paper and an associate professor of rheumatology at Michigan Medicine.

"We’ve now found that this process is exacerbated by the anti-NET antibodies, which disrupt our body’s immune homeostasis during COVID-19 infection."

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Anti-NETs were previously reported in patients with antiphospholipid syndrome by Zuo and the Michigan Medicine team.

The anti-NET antibodies can be associated with the development of recurrent blood clots and more severe disease in antiphospholipid syndrome, said corresponding author Yogen Kanthi, M.D., a cardiologist and vascular medicine specialist at the National Heart, Lung, and Blood Institute and Lasker Investigator at the National Institutes of Health.

"In both diseases, the anti-NET antibodies coat the surface of the neutrophil extracellular traps, making it much harder for the body to clear out this web that causes inflammation and clotting," Kanthi said.

"Knowing their function is likely to help physicians design more targeted COVID-19 treatments and also for other inflammatory diseases."

More study of the virus’ autoimmune aspects, Zuo noted, will not only lead to better understanding of the disease, but will also likely shed light onto the origins of autoimmune diseases.

New study findings may also reveal other COVID mysteries, including the persistence of symptoms in some people months after clearing the virus, a phenomenon known as long COVID, Zuo said.

They are now conducting a follow-up study, calling back patients who were previously hospitalized to repeat testing for the anti-NETs and other autoantibodies that formed during their hospitalizations.

The team will find if and how the autoantibodies influence long COVID, the post-acute sequalae of the virus marked by symptoms like brain fog, fatigue and shortness of breath.

Millions still feel the effects of long COVID, which is why this research is so important, Zuo said.

"The better we understand these COVID-induced autoantibodies such as anti-NET antibodies, the more equipped we will be to fight COVID-19 at every stage of viral infection," Zuo said.

"Studying these antibodies will also teach us about the mechanisms of autoimmunity in general, especially in the field of rheumatology."



Source-Medindia