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The VEXAS Foundation

The VEXAS Foundation is dedicated to improving the lives of patients with VEXAS syndrome by promoting disease awareness, education and the scientific understanding of the diagnosis and treatment of the disease through collaborative research.

VEXAS syndrome has been found to affect approximately 1 in 4,000 men over the age of 50.1  

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What is VEXAS syndrome?

VEXAS syndrome is a newly discovered disease which researchers determined is caused by mutations in UBA1 (a gene found in bone marrow stem cells). The discovery of VEXAS in 2020 illustrates the power of innovations in genomics.2

VEXAS is a chronic, progressive disease estimated to be afflicting hundreds of thousands of people, many of whom have been misdiagnosed. The disease affects multiple organs and causes severe systemic inflammatory and hematologic manifestations.3-5

VEXAS stands for:

  • V Vacuoles are often seen in cells identified in bone marrow biopsies
  • E Abnormally low levels of ubiquitin activating enzyme (E1) result from mutations in UBA1, causing cellular disruption and inflammation
  • The UBA1 gene, which encodes E1, is located on the X chromosome
  • A Patients have severe autoinflammation, meaning there is hyperactivation of immune pathways
  • S The genetic mutations are somatic—acquired at some point in life and not inherited

A Revolutionary Discovery

1990’s-2020
Genetics studies of autoinflammatory and autoimmune disease through biobanking at the National Institutes of Health (NIH)
2020 | October

Discovery of VEXAS syndrome published in the New England Journal of Medicine by Beck, DB et al.3

2021

Identification that UBA1 mutations significantly contribute to various autoimmune diseases, including relapsing polychondritis, amongst other diseases3,5-8

Worldwide recognition of VEXAS syndrome and identification of patients through international collaboration, but lacking effective treatments and standard of care9

2022

Recognized as Year’s Best in Hematology diagnosis at the American Society of Hematology and recognized by the American College of Rheumatology as a clinically important and prevalent disease overlapping many specialties10

New treatments are offered for patients with UBA1 mutations based upon a genetic diagnosis, and clinical trials are initiated at the NIH, but mortality rates remain high 11-15

UBA1 testing is widely available and accessible, decreasing the time between onset of disease and accurate diagnosis
VEXAS Foundation is established

David B. Beck, MD, PhD

David B. Beck, MD, PhD is the principal investigator of the David Beck Lab in the Center for Human Genetics and Genomics and Division of Rheumatology at New York University Grossman School of Medicine. He is internationally recognized for his role in the discovery of VEXAS syndrome and is dedicated to better understanding the mechanism of pathogenesis of VEXAS syndrome and the development of novel treatments for VEXAS and other autoinflammatory diseases, always striving toward improving patient outcomes and quality of life. In response to a growing unmet need, Dr. Beck runs the Inflammatory Diseases Genetics Program at NYU Langone in the Division of Rheumatology and the Center for Human Genetics and Genomics, evidencing his commitment to expanding the scientific understanding of inflammatory disorders and furthering the development of novel therapies using cutting-edge technology.

An alumnus of Brown University, Dr. Beck earned his medical degree and PhD in biochemistry from NYU School of Medicine. Thereafter, he completed his residency in internal medicine at Columbia University and postdoctoral fellowship in clinical genetics with Dr. Dan Kastner at the NIH. Dr. Beck has authored several important studies in high-impact journals and is the recipient of several honors and awards, including the National Human Genome Research Institute Intramural Research Award and the Burroughs Wellcome Fund Career Award for Medical Scientists. Dr. Beck continues advancing patient care by engaging members of the medical community through his lectures about VEXAS at both national and international conferences, disseminating the latest research and clinical findings as a means of providing essential guidance regarding assessment and treatment strategies to those caring for patients with VEXAS.

What are the symptoms of VEXAS syndrome?

Severe inflammatory symptoms that tend to affect multiple organs including:

    • Skin (rashes that may be painful)
    • Cartilaginous structures (pain and swelling of the ear/nose called chondritis)
    • Lungs (cough and shortness of breath)
    • Joints (swelling and pain)
    • Vasculature (inflammation of the blood vessels)

Progression of hematologic manifestations often leading to bone marrow failure:

    • Macrocytic anemia
    • Low blood cell counts
    • Transfusion dependence
    • Hematologic malignancies
Clinical manifestations of VEXAS
Courtesy of Dr. Peter Grayson12

How is VEXAS syndrome diagnosed?

VEXAS is diagnosed by genetic testing of mutations in the UBA1 gene.

When should genetic testing for VEXAS syndrome be considered?

VEXAS should be suspected in a patient who has an overlap of inflammatory and hematologic manifestations.

Since the disease is X linked, it is far more common in males, but females can also have VEXAS.

Patients with VEXAS have elevated inflammatory markers such as C-Reactive Protein (CRP) and Erythrocyte Sedimentation Rate (ESR).

Common diagnoses found in patients with VEXAS include the following: 2-13

    • Hematologic diagnoses:
      • Myelodysplastic syndrome (49%)
      • Multiple myeloma/Monoclonal gammopathy of unknown origin (11%)
      • Cytopenia(s) of an unknown cause
      • Macrocytic anemia (MCV > 100 fL)
      • Thrombocytopenia (platelet count < 200 K/μL )
      • Venous and arterial thrombosis (blood clots)
    • Inflammatory diagnoses:
      • Relapsing polychondritis (49%)
      • Neutrophilic dermatosis/Cutaneous vasculitis (82%)
        • Sweet syndrome
        • Giant cell arteritis
        • Polyarteritis nodosa

Although only a subset of patients with VEXAS have relapsing polychondritis, Ferrada et al.7 developed an algorithm which is a useful tool for identifying those at risk.

In a patient with ear or nose chondritis, VEXAS can be identified with 96% accuracy when the following 3 criteria are met:

    • Male sex; and
    • Mean corpuscular volume > 100 fL; and/or
    • Platelet count < 200 K/μL
MCV = mean corpuscular volume; VEXAS RP = VEXAS with relapsing polychondritis
Courtesy of Dr. Marcela Ferrada

What treatments are available for VEXAS syndrome?

Currently, there is no standardized treatment, available treatments are not curative and mortality from VEXAS remains high. Inflammatory features are typically treated with high-dose glucocorticoids which are associated with significant side effects, causing many complications. Some patients may be candidates for bone marrow transplantation, which can also be associated with significant risks. A clinical trial is currently available at the NIH to evaluate stem cell transplant as a possible treatment for patients with VEXAS.11-13

Patients with VEXAS syndrome can have involvement of multiple organs and are best served by a multidisciplinary approach, typically involving a team of doctors, including a rheumatologist and hematologist.2,3,14,15

The next phase of VEXAS research

The discovery of VEXAS syndrome continues to have a global impact in the medical community and was deemed “this year’s best in hematology diagnosis” by the American Society of Hematology,10 and recognized as a clinically important and prevalent disease across many clinics (rheumatology, hematology and dermatology)2,3,14,15 by the American College of Rheumatology.

With the new understanding that VEXAS is a disease representing an overlap between hematology and rheumatology, researchers are exploring the biology underlying this association and striving to better understand the inflammatory process associated with VEXAS. Through the use of innovative technology, researchers plan to investigate the development of novel therapies. This technology which will likely be applicable to numerous inflammatory diseases, such as systemic lupus erythematous, rheumatoid arthritis and myelodysplastic syndrome, amongst others,3 which likely share similar disrupted processes and symptoms with VEXAS syndrome.

At the forefront of precision medicine and targeted therapies, the VEXAS foundation is partnering with researchers at the David Beck Lab in the Center for Autoimmune and Autoinflammatory Genetic Diseases at NYU Langone, who will be exploring gene therapy approaches to correct for mutations in UBA1. Once successful, the data from these experiments will be used as a stepping stone toward a clinical trial, potentially curing VEXAS and providing data to catapult the discovery of cures for other autoinflammatory diseases. As Dr. Marcela Ferrada, a leading VEXAS expert at The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) reminds patients, “Where there is research, there is hope and we have research!”

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Our research partners

The VEXAS Foundation would like to express its gratitude to Michael Linn and David Bammert of the Relapsing Polychondritis Foundation, for the numerous hours of consultation and generous financial support dedicated to the creation and continued support of the VEXAS Foundation. The revolutionary discovery of VEXAS syndrome demonstrated that autoimmune disorders previously thought to be unrelated to each other, like relapsing polychondritis (RP), polyarteritis nodosa, sweet syndrome, and giant cell arteritis, share a common acquired, somatic mutation in the UBA1 gene.3 Now, the Relapsing Polychondritis Foundation is expanding the impact of the VEXAS discovery by investing in a research project to continue the search for additional genetic mutations in patients with autoimmune and autoinflammatory diseases. Genetic variants will be correlated with the clinical history of the subjects, followed by laboratory-based experiments to determine the mechanism by which these genetic variations lead to systemic inflammation and disease. This project will leverage a collaborative network of talented researchers at NYU Langone and the NIH.

Donate to help find a cure for VEXAS syndrome and simultaneously help to advance treatments for other autoinflammatory and autoimmune diseases

Mail donations to:
VEXAS Foundation Inc.
1202 Lexington Avenue, #112
New York, NY 10028

For questions about making a donation,
including making a donation online, please contact us at:
donate@VEXASfoundation.org

1Beck DB, Bodian DL, Shah V, Mirshahi UL, Kim J, Ding Y, Strande NT, Cantor A, Haley JS, Cook A, Hill W, Grayson PC, Ferrada MA, Kastner DL, Carey DJ, Stewart DR. Genomic ascertainment for UBA1 variants and VEXAS syndrome: a population-based study. medRxiv. 2022. doi:10.1101/2022.07.27.22277962

2Stubbins RJ, Cherniawsky H, Chen LYC, Nevill TJ. Innovations in genomics for undiagnosed diseases: vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome. CMAJ. 2022;194(14):E524-E527. doi:10.1503/cmaj.211770

3Beck DB, Ferrada MA, Sikora KA, et al. Somatic Mutations in UBA1 and Severe Adult-Onset Autoinflammatory Disease. N Engl J Med. 2020;383(27):2628-2638. doi:10.1056/NEJMoa2026834

4Obiorah IE, Patel BA, Groarke EM, et al. Benign and malignant hematologic manifestations in patients with VEXAS syndrome due to somatic mutations in UBA1. Blood Adv. 2021;5(16):3203-3215. doi:10.1182/bloodadvances.2021004976

5Koster MJ, Warrington KJ. VEXAS within the spectrum of rheumatologic disease. Semin Hematol. 2021;58(4):218-225. doi:10.1053/j.seminhematol.2021.10.002

6Koster MJ, Kourelis T, Reichard KK, et al. Clinical Heterogeneity of the VEXAS Syndrome: A Case Series. Mayo Clin Proc. 2021;96(10):2653-2659. doi:10.1016/j.mayocp.2021.06.006

7Ferrada MA, Sikora KA, Luo Y, et al. Somatic Mutations in UBA1 Define a Distinct Subset of Relapsing Polychondritis Patients With VEXAS. Arthritis Rheumatol. 2021;73(10):1886-1895. doi:10.1002/art.41743

8Tsuchida N, Kunishita Y, Uchiyama Y, et al. Pathogenic UBA1 variants associated with VEXAS syndrome in Japanese patients with relapsing polychondritis [published online ahead of print, 2021 Mar 31]. Ann Rheum Dis. 2021;annrheumdis-2021-220089. doi:10.1136/annrheumdis-2021-220089

9Poulter JA, Collins JC, Cargo C, et al. Novel somatic mutations in UBA1 as a cause of VEXAS syndrome. Blood. 2021;137(26):3676-3681

10Hasserjian, R. P., M.D. (2022). This year’s best in hematology diagnosis: A new disease is discovered. The Hematologist, 19(1), 1-8. https://doi.org/10.1182/hem.V19.1.2022117

11A phase II study of allogeneic hematopoietic stem cell transplant for subjects with VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome. NCT05027945

12Grayson PC, Patel BA, Young NS. VEXAS syndrome. Blood. 2021;137(26):3591-3594. doi:10.1182/blood.2021011455

13Sterling D, Duncan ME, Philippidou M, Salisbury JR, Kulasekararaj AG, Basu TN. VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) for the dermatologist [published online ahead of print, 2022 Feb 2]. J Am Acad Dermatol. 2022;S0190-9622(22)00181-5. doi:10.1016/j.jaad.2022.01.042

14Staels F, Betrains A, Woei-A-Jin FJSH, et al. Case Report: VEXAS Syndrome: From Mild Symptoms to Life-Threatening Macrophage Activation Syndrome [published correction appears in Front Immunol. 2021 Aug 10;12:748756]. Front Immunol. 2021;12:678927. Published 2021 Apr 23. doi:10.3389/fimmu.2021.678927

15Ferrada M, Savic S, Alessi H, et al. Genotype and transfusion dependence predicts mortality in VEXAS syndrome, a newly described disease with overlap inflammatory and hematologic features. Presented at: ACR Convergence 2021; November 3-10, 2021. Abstract 143