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<h2 class="element-invisible">You are here</h2><div class="breadcrumb"><a href="/">Home</a> » <a href="/news-events">News & Events</a> » <a href="/news-events/nih-research-matters">NIH Research Matters</a></div> <div class="l-region l-region--section-header">
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<p class="publishdate"><span property="dc:date" datatype="xsd:dateTime" content="2023-02-14T00:00:00-05:00" class="date-display-single">February 14, 2023</span></p><div class='syndicate'><h1>VEXAS syndrome more common than realized</h1><div class="callout callout-with-border"><h3>At a Glance</h3>
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<ul>
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<li>A severe inflammatory disease called VEXAS is more prevalent and has a broader range of symptoms than expected.</li>
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<li>Additional studies of racially diverse populations are needed to better understand the scope and symptoms of this hard-to-recognize disease.</li>
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</ul></div><div class="media-float-right"><div class="ds-1col file file-image file-image-jpeg view-mode-floated_media clearfix">
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<picture title="Older man talking to a doctor">
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<!--[if IE 9]><video style="display: none;"><![endif]-->
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-large/public/news-events/research-matters/2023/20230214-vexas.jpg?itok=B6q99DUB&timestamp=1676312588 1x" media="screen and (min-width: 960px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium/public/news-events/research-matters/2023/20230214-vexas.jpg?itok=J0yeA-Oi&timestamp=1676312588 1x" media="screen and (min-width: 800px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium-small/public/news-events/research-matters/2023/20230214-vexas.jpg?itok=gx30F6CJ&timestamp=1676312588 1x" media="screen and (min-width: 600px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-small/public/news-events/research-matters/2023/20230214-vexas.jpg?itok=9fSYvm0m&timestamp=1676312588 1x" media="screen and (min-width: 480px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-tiny/public/news-events/research-matters/2023/20230214-vexas.jpg?itok=s9BYRxwp&timestamp=1676312588 1x" media="screen and (min-width: 0)" />
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<!--[if IE 9]></video><![endif]-->
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<img src="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium/public/news-events/research-matters/2023/20230214-vexas.jpg?itok=J0yeA-Oi&timestamp=1676312588" alt="Older man talking to a doctor" title="Older man talking to a doctor" />
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</picture><span class="caption">The study suggests that VEXAS disease, which was only recently discovered, may be more common than previously thought. </span><span class="credit">Lucky Business / Shutterstock</span></div>
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</div><p>In 2020, a team of NIH researchers <a href="https://www.nih.gov/news-events/nih-research-matters/new-inflammatory-disease-discovered">reported the discovery</a> of a rare and often-deadly inflammatory disorder, which they named VEXAS. Affected people have varying symptoms that can include anemia, recurrent fevers, painful rashes, blood clots, and shortness of breath. Because these symptoms overlap with other autoimmune and inflammatory diseases, VEXAS can be hard to recognize. But having an accurate diagnosis is important for effective treatment.</p>
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<p>VEXAS was discovered by searching for genetic variants that were shared among more than 2,500 patients with body-wide inflammation or other unusual and undiagnosed conditions. The identified gene, <em>UBA1, </em>is on the X chromosome, and all 25 people initially diagnosed with VEXAS were male. Since men have only one X chromosome, they only have one copy of the gene. Women typically have two X chromosomes and therefore two copies of <em>UBA1. </em>In women, a mutation in only one copy is likely to cause less severe or no disease. The genetic mutations that cause this disease occur after birth and so aren’t transmitted from parents to children.</p>
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<p>A research team set out to assess the symptoms and prevalence of VEXAS-related variants in a larger population. The group was led by Dr. David Beck of New York University, in collaboration with Drs. Jung Kim and Douglas Stewart of NIH’s National Cancer Institute. The scientists combed through data from more than 160,000 patients in a regional health care system in Pennsylvania. All had agreed to have their DNA screened. Participants were predominantly white (94%, which roughly matches regional demographics), and more than half were women (61%). The mean age of participants was 53. Results appeared online in <em>JAMA </em>on January 24, 2023.</p>
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||
<p>Genetic analysis revealed that 12 of the participants (or 1 in 13,591 people) appeared to have disease-related variants in <em>UBA1.</em> Ten were men and two were women. Health records showed that all 12 had symptoms consistent with VEXAS, including a range of autoimmune, lung, or skin abnormalities. </p>
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||
<p>By closely examining the 12 participants’ medical records, the researchers found that <em>UBA1 </em>variants led to a broader range of symptoms than originally thought. “Classic” symptoms of VEXAS were also sometimes absent. The researchers note that a diagnosis based on symptoms alone could easily miss cases of VEXAS that would be caught by <em>UBA1 </em>testing.</p>
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<p>“Our study offers the first glimpse of just how common VEXAS syndrome is in the United States, particularly among men, who also happen to be the most likely to die from it,” Beck says. “Now that we know VEXAS syndrome is more common than many other types of rheumatologic conditions, physicians need to add this condition to their list of potential diagnoses when confronted by patients with persistent and unexplained inflammation and low blood cell counts, or anemia.”</p>
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<p>The team now aims to conduct similar studies among more racially diverse groups to gain a clearer picture of who’s most at-risk for developing VEXAS. “In addition, there are other genes that may be associated with inflammatory disorders like VEXAS,” Stewart says. “The team is investigating if mutations in those genes are linked to VEXAS-like medical problems for the people who harbor those variants.”</p>
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<p>—by Vicki Contie</p></div><h2 class="label-above">Related Links</h2><ul class="spaced print-urls"><li><a href="https://www.nih.gov/news-events/nih-research-matters/new-inflammatory-disease-discovered" target="_top">New Inflammatory Disease Discovered</a></li><li><a href="https://newsinhealth.nih.gov/2022/06/understanding-autoimmune-diseases" target="_top">Understanding Autoimmune Diseases: When Your Body Turns Against You</a></li><li><a href="https://www.niams.nih.gov/labs/grayson-lab/vexas" target="_top">What is VEXAS syndrome? </a></li><li><a href="https://www.niams.nih.gov/health-topics/autoinflammatory-diseases" target="_top">Autoinflammatory Diseases</a></li><li><a href="https://www.niehs.nih.gov/health/topics/conditions/inflammation/index.cfm" target="_top">Inflammation</a></li></ul><p class="footnote"><strong class="label-inline">References: </strong><a href="https://pubmed.ncbi.nlm.nih.gov/36692560/">Estimated Prevalence and Clinical Manifestations of UBA1 Variants Associated With VEXAS Syndrome in a Clinical Population.</a> Beck DB, Bodian DL, Shah V, Mirshahi UL, Kim J, Ding Y, Magaziner SJ, Strande NT, Cantor A, Haley JS, Cook A, Hill W, Schwartz AL, Grayson PC, Ferrada MA, Kastner DL, Carey DJ, Stewart DR. <em>JAMA.</em> 2023 Jan 24;329(4):318-324. doi: 10.1001/jama.2022.24836. PMID: 36692560.</p><p class="footnote"><strong class="label-inline">Funding: </strong>NIH’s National Cancer Institute (NCI), National Human Genome Research Institute (NHGRI), National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), and National Institute of General Medical Sciences (NIGMS); Relapsing Polychondritis Foundation.</p>
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<div about="/block/research-matters---popular-stori" class="ds-1col entity entity-bean bean-research-matters-block view-mode-default clearfix">
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<p><a href="https://www.nih.gov/news-events/nih-research-matters/research-context-can-we-slow-aging">Research in Context: Can we slow aging?</a></p>
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<p><a href="https://www.nih.gov/news-events/nih-research-matters/brain-changes-observed-during-pregnancy">Brain changes observed during pregnancy</a></p>
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<p><a href="https://www.nih.gov/news-events/nih-research-matters/research-context-detecting-cancer">Research in Context: Detecting cancer</a></p>
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<p><a href="https://www.nih.gov/news-events/nih-research-matters/risk-future-burden-dementia-united-states">Risk and future burden of dementia in the United States </a></p>
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||
|
||
<p><a href="https://www.nih.gov/news-events/nih-research-matters/complete-wiring-map-adult-fruit-fly-brain">Complete wiring map of an adult fruit fly brain</a></p>
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<h3 class="block__title">About NIH Research Matters</h3>
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<p><strong>Editor:</strong> Harrison Wein, Ph.D.</p>
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<p><strong>Assistant Editors:</strong> Vicki Contie and Brian Doctrow, Ph.D.</p>
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<p><strong><em>NIH Research Matters </em></strong>is a weekly update of NIH research highlights reviewed by NIH’s experts. It's published by the <a href="/institutes-nih/nih-office-director/office-communications-public-liaison">Office of Communications and Public Liaison</a> in the <a href="/institutes-nih/nih-office-director">NIH Office of the Director</a>.</p>
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<p>ISSN 2375-9593</p>
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