Researchers Discover New Inflammatory Syndrome

The overlap in symptoms of chronic inflammatory diseases can make diagnosing many cases difficult. The rarer the condition, the less likely the sufferer is of ever putting a name to it. But the recent discovery of a new inflammatory syndrome could mean real answers for some. Here’s what we know so far.

The VEXAS Discovery

Researchers at the National Human Genome Research Institute, a branch of the National Institutes of Health (NIH), recently studied the genes of over 2,500 people suffering from undiagnosed inflammatory disorders. They pinpointed the cause of one condition to a mutation in the UBA1 gene, which is on the X chromosome.

According to their article, which appeared in The New England Journal of Medicine, researchers were able to connect the gene mutation to a set of symptoms clustered in 25 of the study’s participants. The disorder has been dubbed VEXAS, an acronym for its five diagnostic markers. They include:

• Vacuoles, or pockets of fluid, being present in specific types of cells;
• E1 enzyme deficiency, a major factor in symptom presentation;
• X-chromosome mutation;
• Autoinflammatory condition;
• Somatic symptoms, including fevers, changes in blood cell counts and inflammation of the blood vessels, skin, lungs and cartilage. 

Research on zebrafish helped to pinpoint the responsible gene. The animals have several that are remarkably similar to ours; their UBA1 gene appears to have the same functions as our UBA1 gene. Zebrafish bred to be missing UBA1 (to mimic the improperly functioning mutated UBA1 in humans) developed inflammation and died much younger than those with working UBA1 genes.

VEXAS appears to affect exclusively middle-aged men, with an average onset age of 64. Of the 25 participants, 10 had already died before the NIH study began, leading researchers to believe the condition likely also has serious impacts on life expectancy.

Why Men?

It might seem strange at first that a mutation on the X chromosome is responsible for a condition that only affects men, but it actually makes sense a lot of sense. Physician’s Weekly explains that typical males each receive one X chromosome, so if the UBA1 gene on that chromosome mutates, the mutation fully expresses. The condition appears to affect middle-aged men specifically because the mutation is more likely to occur in older individuals.

Because women have two X chromosomes, two copies of the UBA1 gene are present, one from the mother and one from the father. So, if one happens to mutate, it still must compete with the non-mutated version from the other X chromosome. For this reason, it may be possible that many women also suffer from a milder form of the condition, although more research is needed to determine specific disease presentation.

VEXAS is just one of countless conditions that have perplexed the medical community and frustrated patients for decades but here we are, finally finding some answers — and that gives us hope for the future of these conditions as each discovery often opens up new avenues for research leading to even more breakthroughs. More answers mean more opportunities for solutions, so every step forward is a step in the right direction.

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