A team of scientists from the US National Institutes of Health (NIH) have identified a previously unknown inflammatory disease that exclusively affects males. It is a genetic syndrome called VEXAS.
Men with this auto-inflammatory disease have symptoms including unexplained fevers, blood clots, and inflammations of cartilage, lung tissue, and blood vessels. The condition has been shown lethal in 40% of known cases.
To identify the disease, NIH researchers worked the other way around: instead of grouping people with similar symptoms and looking for biological explanations, they examined the genetic makeup of 2,560 people to find possible variations that might be related to the symptoms of their unexplained inflammatory conditions.
“We had many patients with undiagnosed inflammatory conditions who were coming to the NIH Clinical Center, and we were just unable to diagnose them. That’s when we had the idea of doing it the opposite way. Instead of starting with symptoms, start with a list of genes. Then, study the genomes of undiagnosed individuals and see where it takes us”says David Beck, lead author of the study, published in the New England Journal of Medicine
As part of genetic research, scientists identified three middle-aged men who had the same mutations in a gene called UBA1. Subsequently, 22 other men were discovered with the same mutations and similar symptoms.
Researchers named the new disease VEXAS, an acronym based on its key characteristics: Vacuoles, enzyme E1, linked to the X chromosome, auto-inflammatory and somatic.
Vacuoles are cavity-shaped structures, similar to bubbles. In men with VEXAS syndrome, they are found in certain blood cells.
E1 is an enzyme related to the UBA1 gene, where mutations that cause the newly discovered disease are found.
Researchers suspect that VEXAS affects only men because it is linked to the X chromosome. They hypothesize that women’s additional X chromosome could somehow nullify the mutation and have a protective effect.
The fact that it is an autoinflammatory condition means that the patient’s immune system accidentally attacks their own body. Being a somatic condition means that the disease occurs at some point throughout a person’s life, that is, it is not a birth syndrome.
Since the research was published, 25 more patients with VEXAS syndrome have been diagnosed. The study authors believe, however, the number of individuals with the disease is much higher. In the US alone, about 125 million people have a chronic inflammatory condition.