VEXAS Syndrome Prevalence in America

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Definition

VEXAS Syndrome

VEXAS syndrome is a disease that causes inflammatory and hematologic (blood) manifestations. VEXAS is an acronym that stands for the technical terms of key descriptors of the condition.

• V - Vacuoles are often identified in the bone marrow stem cells of patients presenting with VEXAS.
• E - E1 ubiquitin-conjugating enzyme encoded by the UBA1 gene is mutated in patients.
• X - X-chromosome. Mutated UBA1 gene is located on the X-chromosome - the disease is almost exclusively found in people with XY chromosomes and is said to be X-linked.
• A - Autoinflammatory patients with VEXAS present with a wide array of Autoinflammatory conditions.
• S: Somatic, the mutations which cause VEXAS are Somatic; they are acquired throughout life, not inherited, and unable to be passed onto offspring.

The syndrome is caused by mutations in the UBA1 gene of blood cells and acquired later in life. Normally, inflammation is an immune system response to injury or foreign invaders (such as bacteria). In people with VEXAS syndrome, part of the immune system called the innate immune response is activated abnormally when there is no injury or foreign invader, which causes fevers and inflammation-related damage to tissues and organs. Based on this process, VEXAS syndrome is classified as an autoinflammatory disease. Patients do not pass the disease to their children.

Main Digest

Estimated Prevalence and Clinical Manifestations of UBA1 Variants Associated with VEXAS Syndrome in a Clinical Population - People

About 13,200 men and another 2,300 women in the United States over 50 are estimated to have VEXAS syndrome, according to a new study. Long considered a mystery illness until its genetic basis was identified in 2020, the latest findings, led by researchers at NYU Grossman School of Medicine, offer the first indication of how common the illness is domestically.

Although a rare disorder, the syndrome carries a high mortality rate, with up to half of people, mostly men, dying within five years of diagnosis. The syndrome most often involves unexplained fevers and low blood oxygen levels in people diagnosed with other diseases, such as rheumatoid arthritis, lupus, and blood cancer. Some of the symptoms have been linked to an overactive immune system, which can cause inflammation and classifies the syndrome as an autoimmune condition.

Researchers hope their findings will raise awareness of the disorder among physicians, particularly because high-dose steroids, JANUS kinase inhibitors, and bone marrow transplantation have proven effective in controlling some symptoms.

"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," says geneticist and study lead investigator David Beck, MD, Ph.D. Beck, an assistant professor in the Department of Medicine and the Department of Biochemistry and Molecular Pharmacology at NYU Langone Health, also led the federal research team that initially identified the shared UBA1 mutation among VEXAS patients.

In the new study published in the Journal of the American Medical Association (JAMA) online on Jan. 24, researchers analyzed the electronic health records of 163,096 mostly white men and women in Pennsylvania who agreed to have their blood DNA screened for signs of genetic disease. Twelve were found to have the UBA1 mutation, with all experiencing VEXAS symptoms.

Statistically, this corresponded to one in 4,269 American men over age 50 and one in 26,238 women over age 50 having or are likely to develop the syndrome. Researchers say this is a higher prevalence figure than many other inflammatory conditions, including vasculitis and myeloid dysplasia syndrome.

"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 to die from it," says Beck, who is leading several clinical research efforts into VEXAS syndrome at NYU Langone's Center for Human Genetics and Genomics.

Previous research, led by Beck, traced the syndrome's origins to a mutation, or change in the letter code that makes up DNA, in the gene UBA1 (short for ubiquitin-like modifier activating enzyme 1.) The enzyme usually assists in protein breakdown.

VEXAS stands for many of its biological characteristics: vacuoles in blood cells, the E1 enzyme, X-linked, autoinflammatory, and somatic.

For the study, researchers analyzed the electronic medical records of adult patients who volunteered to participate in the Geisinger MyCode Community Health Initiative. The program has collected data for more than 25 years from patients in Geisinger's 10-plus hospitals in Central and Northeastern Pennsylvania. Almost all study participants who agreed to have their blood DNA tested were white; half were over the age of 60.

Beck says the team next plans to analyze patient records in more racially diverse groups, especially among those with higher rates of rheumatologic and blood disease, to gain a more precise picture of who is most at risk of VEXAS syndrome. They also plan to look for additional genetic causes, test new therapies for the syndrome, and develop a simple blood test for UBA1 to make it easier to diagnose.

Funding

Funding for the study was provided by National Institute of Health grants R00AR078205 and T32GM136542.

Research

Besides Beck, other NYU Langone researchers involved in this study are Samuel Magaziner, MPhil; and Ann Cantor, MS. Other study co-investigators are Dale Bodian, Ph.D., at Geisinger Research in North Bethesda, Md.; Vandan Shah, MD; Uyenlinh Mirshahi, Ph.D.; Natasha Strande Ph.D.; Jeremy Haley, MS; Adam Cook, MS; Wesley Hill; Yi Ding, MD, Ph.D.; and David Carey, Ph.D., at Geisinger Health in Danville, Pa.; Jung Kim, Ph.D., and Douglas Stewart, at the National Cancer Institute in Rockville, Md.; Alan Schwartz, MD, Ph.D., at the University of Washington in St. Louis, Mo.; Peter Grayson, MD, and Marcela Ferrada, MD, at the National Institute of Arthritis and Musculoskeletal and Skin Diseases in Bethesda; and Daniel Kastner, MD, at the National Human Genome Research Institute, also in Bethesda.

Attribution/Source(s):

This peer reviewed article relating to our Autoimmune Diseases section was selected for publishing by the editors of Disabled World due to its likely interest to our disability community readers. Though the content may have been edited for style, clarity, or length, the article "VEXAS Syndrome Prevalence in America" was originally written by NYU Langone Health / NYU Grossman School of Medicine, and published by Disabled-World.com on 2023/01/24. Should you require further information or clarification, NYU Langone Health / NYU Grossman School of Medicine can be contacted at nyulangone.org. Disabled World makes no warranties or representations in connection therewith.

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