VEXAS syndrome in men is more common than previously thought

A rare disease, first identified in 2020, is far more common than thought, say University of Leeds researchers studying its origins.

VEXAS syndrome is a serious inflammatory condition that develops in men over 50 that causes them to become very sick, tired and can be fatal. It was originally considered rare, but a new study has identified genetic mutations that suggest the disease is actually much more common.

Researchers developed a genetic test to identify patients who may have the disease and now want to examine more people with symptoms to understand exactly how common they are.

VEXAS syndrome causes unexplained fevers, painful rashes, and affects the bone marrow, resulting in decreased red and white blood cell counts. The disease only affects men as it is caused by genetic mutations on the X chromosome and men only have one X chromosome. The mutations are not present at birth, but develop during the patient’s lifetime.

The disease was identified in 2020 by a team of researchers including Dr. Sinisa Savic, Clinical Associate Professor in the University of Leeds School of Medicine and Honorary Consultant Immunologist at NHS Teaching Hospitals in Leeds. Further research in Leeds carried out by Dr. Savic and Dr. James Poulter, Research Associate in Molecular Neuroscience at the School of Medicine, identified additional genetic mutations that reveal new ways the disease can develop.

The team, which included 13 scientists and clinicians from Leeds, Hull, York and the United States, examined DNA samples to determine the prevalence of the genetic mutations identified when the disease was first discovered.

Dr. Poulter said, “In our new study, we looked at a cohort of 18 local patients who matched the symptoms and found mutations in 10. Eight had the known variant that was previously associated with the disease, but two patients had completely different variants. This identified a new way in which the mutations can cause VEXAS, which means it’s likely a lot more common than we currently think.

“We want to examine more people with these symptoms to really understand how common VEXAS is and to better understand the disorder.

“Most patients have had a lot of tests, tried many treatments and couldn’t get an answer to what they have. Now, by sequencing their DNA for mutations in the VEXAS gene, we can identify those patients who have VEXAS and get the best one available treatment. This could be a bone marrow transplant or a switch to another drug. “

Dr. Savic heads a specialist allergy and clinical immunology service at the Leeds Trusting Hospitals NHS Trust. It is one of four centers in the UK that is part of the European Reference Network for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases.

I have been caring for a number of patients with what is now known as VEXAS syndrome for several years. Her care was made difficult by the fact that we did not have a diagnosis, which made it very difficult to choose her treatment and advise her on the prognosis.

Now that we have identified the cause of VEXAS, we now have a real chance to transform the way we care for these patients. We know that there are still many patients who have VEXAS-like disease but we do not know the cause. We plan to continue our research in hopes of discovering other genetic causes of these disorders. “

Dr. Sinisa Savic, Clinical Associate Professor in the University of Leeds School of Medicine

Source:

Journal reference:

JA Poulter et al. (2021) Novel somatic mutations in UBA1 as the cause of the VEXAS syndrome. Blood. doi.org/10.1182/blood.2020010286.

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