Genetic Study Uncovers New Inflammatory Disease Affecting Men

Chronic inflammatory diseases affect nearly 125 million people in the United States. A recent study from the National Institutes of Health (NIH) discovered a new disease that genetically affects men.

A recent paper was published in The New England Journal of Medicine describing the new chronic inflammatory disease called vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome, or VEXAS. The disease is caused by mutations in the UBA1 gene which is responsible for regulating proteins.

Symptoms of VEXAS include blood clots in veins, fever, and abnormalities in the lungs, or myeloid cells. Myeloid cells are blood cells found in the bone marrow.

During the study, the research team studied the genetics of 2,560 people for factors indicating inflammatory conditions. Dr. David Beck said, "We had many patients with undiagnosed inflammatory conditions who were coming to the NIH Clinical Center, and we were just unable to diagnose them." More than 1,000 patients remained undiagnosed but had symptoms of inflammation and recurrent fevers.

New Genetic Disease

The genetic disease may be affecting at least hundreds of men in the United States, according to the researchers. 40% of the patients in the study have died, revealing how severe the disease affects men.

At first, three middle-aged men were identified to have the same genetic mutations in the UBA1 by having two copies of the gene and a third copy that was mutated. Typically, humans have only two copies of every gene. Later on, 22 other men had the same genetic mutation and similar symptoms, who all remained undiagnosed.

According to their results, VEXAS may be affecting men since they only have one X chromosome. The additional X chromosome that women have may be protecting them from the genetic disease, suspect the researchers.

Dr. Beck explained that it was a possible sign of mosaicism or groups of cells with mutations that are unique. It was also possible that the VEXAS patients had cells that carried normal UBA1 genes and other cells with the mutated copy.

After the paper was published, 25 more patients were identified to have the same condition. Dr. Ephrat Levy-Lahad and Mary-Claire King, who wrote an editorial to the study but weren't involved in the research, shared that the discovery is important for rheumatologists.

Genomic-First Strategy

The team also uncovered the importance of using a genomic strategy to identify genetic conditions instead of grouping patients according to similar symptoms. This is especially difficult for those with the chronic inflammatory disease since many symptoms overlap with two or more diseases, resulting in patients left undiagnosed for a specific disease.

They hope that the new research will help diagnose and treat patients with inflammatory disease and also improve the classification of those conditions. Patients with mysterious symptoms who are looking for effective treatments would also benefit from the genetic study.

Dr. Natalie Azar from New York University Langone said that rheumatologists don't have a diagnosis for their patients. The new research "opens up a whole world of potential therapeutics down the line."

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