Researchers from the University of San Diego (US) have joined forces with researchers from the UK in a retrospective observational study to investigate a Covid-related syndrome after noticing that some patients had a very rare autoimmune disease called MDA5: dermatomyositis (DM). associated with autoantibodies in patients who may or may not have Covid.”
The researchers wanted to know if there was a link between MDA5-positive dermatomyositis and COVID-19. “Diabetes is more common among people of Asian descent, especially Japanese and Chinese,” says Pradipta Ghosh of the University of California San Diego School of Medicine. “However, Dr. McGonagle was noticing this exploding trend of cases among Caucasians,” he adds.
“BoNE is designed to ignore factors that differentiate patients in the group while selectively identifying what is common (shared) among all members of the group,” Ghosh explained. Previous applications of BoNE have allowed Ghosh and his team to identify other COVID-associated pulmonary and cardiac syndromes in adults and children, respectively.
Ghosh and Denis McGonagle, a professor of rheumatology research at the University of Leeds in the UK, formed a team to investigate what they found was in fact an entirely new syndrome.
The study began with the McGonagle lab's discovery of autoantibodies against MDA5, an RNA-sensing enzyme whose functions include detecting COVID-19 and other RNA viruses. A total of 25 patients in the group of 60 developed lung scarring, also known as interstitial lung disease. Lung scarring was severe enough to cause eight people in the group to die from progressive fibrosis, Ghosh noted. He said there are consistent clinical features of MDA5 autoimmune diseases.
Ghosh and the UC San Diego team explored McGonagle's data with BoNE. They found that patients who showed the highest level of MDA5 response also showed high levels of interleukin 15.
“Interleukin-15 is a cytokine that can trigger two main types of immune cells,” he explains. “This can push cells to the brink of exhaustion and create an immune phenotype that is often seen as a hallmark of progressive interstitial lung disease or lung fibrosis,” he adds.
BoNE allowed the team to determine the cause of Yorkshire Syndrome and identify specific single nucleotide polymorphisms that have a protective effect. With the discovery, the group was able to give a name to the disease: MDA5-autoimmune interstitial pneumonia associated with COVID-19. It's MIP-C for short, “pronounced 'mipsy,'” Ghosh said, adding that the name was coined to connect the connection with MIS-C, a separate childhood condition associated with COVID-19.
Ghosh says MIP-C is unlikely to be limited to the UK. Reports of MIP-C symptoms come from all over the world. He notes that he hopes the team's identification of interleukin-15 as a causal link will stimulate research into a treatment.
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