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Wikipedia

VEXAS syndrome

January 07, 2023

VEXAS syndrome is an adult-onset autoinflammatory disease primarily affecting males, caused by a somatic mutation of the UBA1 gene in hematopoietic progenitor cells.[1][2][3][4][5] The name VEXAS is an acronym deriving from the core features of disease:[6]

V: Vacuoles are often identified in the bone marrow stem cells of patients presenting with VEXAS.

E: The E1 ubiquitin conjugating enzyme encoded by the UBA1 gene is mutated in patients.

X: The mutated UBA1 gene is located on the X-chromosome and thus the disease is almost exclusively found in individuals with XY chromosomes and thus said to be X-linked.

A: Patients with VEXAS present with a wide array of Autoinflammatory conditions

S: The mutations which cause VEXAS are Somatic, meaning that they are acquired throughout life, not inherited, and unable to be passed onto one's offspring.

Signs and Symptoms

The disease arises in late adulthood (typically after the age of 50) and causes both autoinflammatory and hematologic symptoms.[7] Fever and skin conditions—particularly rashes resembling those seen in Sweet syndrome—are common signs. Other autoinflammatory conditions that can occur in individuals with VEXAS syndrome include periorbital angioedema, uveitis and scleritis, relapsing polychondritis, and polyarteritis nodosa. Inflammation may also affect the lungs.[7][8] Hematologic issues include macrocytic anemia, a low platelet count, and a predisposition towards developing hematologic malignancies, especially myelodysplastic syndrome. On bone marrow examination, people with the disease exhibit abnormal vacuoles in precursor cells of the myeloid and erythroid lineages.[7]

Treatment

VEXAS syndrome becomes more severe over time and carries a high mortality rate. Symptoms can be managed with high-dose corticosteroid therapy, but this can cause serious adverse effects, and symptoms typically recur after the dosage is lowered. For this reason, a variety of alternative treatments are under investigation.[7][8] The molecular mechanism of VEXAS is currently unknown.

History and Discovery

The syndrome was identified by a multidisciplinary team of clinicians and scientists led David B. Beck, Peter Grayson, and Daniel L. Kastner.[9][10] It was first reported in The New England Journal of Medicine in October 2020 where Beck et al wrote: "Using a genotype-driven approach, we identified a disorder that connects seemingly unrelated adult-onset inflammatory syndromes".[9] An editorial in the same issue describes the work as a "fascinating discovery" which "is of immediate importance to rheumatologists and has far-reaching consequences of general clinical interest. It builds on previous findings suggesting that postzygotic somatic mutation may be a more frequent cause of human disease than previously recognized".[11]

In 2022, the American Society of Hematology deemed the discovery of VEXAS the "year’s best advancement in hematology-related diagnoses", citing how researching VEXAS will potentially improve the classification of hematologic (blood-based) and adult-onset recurrent autoimmune diseases like relapsing polychondritis.[12]

Ongoing Investigation

Since VEXAS was first described in 2020, there has been global interest in understanding the disease. In 2022 the National Cancer Institute announced a three-year clinical trial to evaluate stem cell transplant as a possible treatment for patients with VEXAS.[13] Scientists, including one of the original discovers David B. Beck, at the New York University Grossman School of Medicine and NYU Langone Health are also actively researching the condition.[14][15][16][17]

References

  1. ^ Onuora, Sarah (1 December 2020). "Somatic mutations cause VEXAS syndrome". Nature Reviews Rheumatology. 17 (1): 1. doi:10.1038/s41584-020-00559-x. ISSN 1759-4790. PMID 33262468.
  2. ^ Mathews, Stephanie (4 November 2020). "NIH Researchers Discover a New Inflammatory Disease Called VEXAS". National Institute of Arthritis and Musculoskeletal and Skin Diseases. from the original on 10 November 2020. Retrieved 17 November 2020.
  3. ^ Edwards, Erika (27 October 2020). "'The VEXAS syndrome': Scientists discover a rare and deadly inflammatory disorder in men". NBC News. Retrieved 17 November 2020.
  4. ^ "New inflammatory disease discovered". NIH Research Matters. National Institutes of Health. 3 November 2020. from the original on 1 December 2020. Retrieved 27 November 2020.
  5. ^ Nelson, Bryn (14 December 2020). "VEXAS: A Newly Identified & Vexing Myeloid-Driven Inflammation". The Rheumatologist. from the original on 19 December 2020. Retrieved 16 December 2020.
  6. ^ Ganguly, Prabarna (27 October 2020). "Scientists use clues in the human genome to discover new inflammatory syndrome". Genome.gov. National Human Genome Research Institute. from the original on 5 November 2020. Retrieved 17 November 2020.
  7. ^ a b c d Grayson, PC; Patel, BA; Young, NS (2021). "VEXAS syndrome". Blood. 137 (26): 3591–3594. doi:10.1182/blood.2021011455. PMC 8462403. PMID 33971000.
  8. ^ a b Sterling, D; Duncan, ME; Philippidou, M; Salisbury, JR; Kulasekararaj, AG; Basu, TN (2022). "VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) for the dermatologist". Journal of the American Academy of Dermatology. doi:10.1016/j.jaad.2022.01.042. PMID 35121074. S2CID 246498890.
  9. ^ a b Beck, David B.; Ferrada, Marcela A.; Sikora, Keith A.; Ombrello, Amanda K.; Collins, Jason C.; Pei, Wuhong; et al. (27 October 2020). "Somatic Mutations in UBA1 and Severe Adult-Onset Autoinflammatory Disease". New England Journal of Medicine. 383 (27): 2628–2638. doi:10.1056/NEJMoa2026834. PMC 7847551. PMID 33108101.
  10. ^ Azvolinsky, Anna (February 2022). "The Vexing VEXAS Syndrome". ASH Clinical News. Retrieved 18 July 2022.
  11. ^ Levy-Lahad, Ephrat; King, Mary-Claire (27 October 2020). "Hiding in Plain Sight — Somatic Mutation in Human Disease". New England Journal of Medicine. 383 (27): 2680–2682. doi:10.1056/NEJMe2030754. PMID 33108100. S2CID 225083761.
  12. ^ Hasserjian, Robert P. (7 January 2022). "This Year's Best in Hematology Diagnosis: A New Disease Is Discovered". The Hematologist. 19 (1). doi:10.1182/hem.V19.1.2022117. ISSN 1551-8779.
  13. ^ "A Phase II Study of Allogeneic Hematopoietic Stem Cell Transplant for Subjects With VEXAS (Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic) Syndrome". clinicaltrials.gov. 14 July 2022. Retrieved 18 July 2022.
  14. ^ Relapsing Polychondritis Foundation (31 March 2022). "The Relapsing Polychondritis Foundation Invests in the Next Phase of VEXAS Research". polychondritis.org. Retrieved 18 July 2022.
  15. ^ Bammert, David (22 June 2022). "The Relapsing Polychondritis Foundation Invests in Potentially Groundbreaking Collaborative Research". Relapsing Polychondritis. Relapsing Polychondritis Foundation. Retrieved 19 July 2022.{{cite web}}: CS1 maint: date and year (link)
  16. ^ Beck, David B.; Werner, Achim; Kastner, Daniel L.; Aksentijevich, Ivona (2022-05-06). "Disorders of ubiquitylation: unchained inflammation". Nature Reviews. Rheumatology. 18 (8): 435–447. doi:10.1038/s41584-022-00778-4. ISSN 1759-4804. PMC 9075716. PMID 35523963.
  17. ^ "Research". davidbecklab.org. Daivd B. Beck Laboratory. 1 July 2022. Retrieved 19 July 2022.

External links

January 07, 2023
vexas, syndrome, adult, onset, autoinflammatory, disease, primarily, affecting, males, caused, somatic, mutation, uba1, gene, hematopoietic, progenitor, cells, name, vexas, acronym, deriving, from, core, features, disease, vacuoles, often, identified, bone, ma. VEXAS syndrome is an adult onset autoinflammatory disease primarily affecting males caused by a somatic mutation of the UBA1 gene in hematopoietic progenitor cells 1 2 3 4 5 The name VEXAS is an acronym deriving from the core features of disease 6 V Vacuoles are often identified in the bone marrow stem cells of patients presenting with VEXAS E The E1 ubiquitin conjugating enzyme encoded by the UBA1 gene is mutated in patients X The mutated UBA1 gene is located on the X chromosome and thus the disease is almost exclusively found in individuals with XY chromosomes and thus said to be X linked A Patients with VEXAS present with a wide array of Autoinflammatory conditionsS The mutations which cause VEXAS are Somatic meaning that they are acquired throughout life not inherited and unable to be passed onto one s offspring Contents 1 Signs and Symptoms 2 Treatment 3 History and Discovery 4 Ongoing Investigation 5 References 6 External linksSigns and Symptoms EditThe disease arises in late adulthood typically after the age of 50 and causes both autoinflammatory and hematologic symptoms 7 Fever and skin conditions particularly rashes resembling those seen in Sweet syndrome are common signs Other autoinflammatory conditions that can occur in individuals with VEXAS syndrome include periorbital angioedema uveitis and scleritis relapsing polychondritis and polyarteritis nodosa Inflammation may also affect the lungs 7 8 Hematologic issues include macrocytic anemia a low platelet count and a predisposition towards developing hematologic malignancies especially myelodysplastic syndrome On bone marrow examination people with the disease exhibit abnormal vacuoles in precursor cells of the myeloid and erythroid lineages 7 Treatment EditVEXAS syndrome becomes more severe over time and carries a high mortality rate Symptoms can be managed with high dose corticosteroid therapy but this can cause serious adverse effects and symptoms typically recur after the dosage is lowered For this reason a variety of alternative treatments are under investigation 7 8 The molecular mechanism of VEXAS is currently unknown History and Discovery EditThe syndrome was identified by a multidisciplinary team of clinicians and scientists led David B Beck Peter Grayson and Daniel L Kastner 9 10 It was first reported in The New England Journal of Medicine in October 2020 where Beck et al wrote Using a genotype driven approach we identified a disorder that connects seemingly unrelated adult onset inflammatory syndromes 9 An editorial in the same issue describes the work as a fascinating discovery which is of immediate importance to rheumatologists and has far reaching consequences of general clinical interest It builds on previous findings suggesting that postzygotic somatic mutation may be a more frequent cause of human disease than previously recognized 11 In 2022 the American Society of Hematology deemed the discovery of VEXAS the year s best advancement in hematology related diagnoses citing how researching VEXAS will potentially improve the classification of hematologic blood based and adult onset recurrent autoimmune diseases like relapsing polychondritis 12 Ongoing Investigation EditSince VEXAS was first described in 2020 there has been global interest in understanding the disease In 2022 the National Cancer Institute announced a three year clinical trial to evaluate stem cell transplant as a possible treatment for patients with VEXAS 13 Scientists including one of the original discovers David B Beck at the New York University Grossman School of Medicine and NYU Langone Health are also actively researching the condition 14 15 16 17 References Edit Onuora Sarah 1 December 2020 Somatic mutations cause VEXAS syndrome Nature Reviews Rheumatology 17 1 1 doi 10 1038 s41584 020 00559 x ISSN 1759 4790 PMID 33262468 Mathews Stephanie 4 November 2020 NIH Researchers Discover a New Inflammatory Disease Called VEXAS National Institute of Arthritis and Musculoskeletal and Skin Diseases Archived from the original on 10 November 2020 Retrieved 17 November 2020 Edwards Erika 27 October 2020 The VEXAS syndrome Scientists discover a rare and deadly inflammatory disorder in men NBC News Retrieved 17 November 2020 New inflammatory disease discovered NIH Research Matters National Institutes of Health 3 November 2020 Archived from the original on 1 December 2020 Retrieved 27 November 2020 Nelson Bryn 14 December 2020 VEXAS A Newly Identified amp Vexing Myeloid Driven Inflammation The Rheumatologist Archived from the original on 19 December 2020 Retrieved 16 December 2020 Ganguly Prabarna 27 October 2020 Scientists use clues in the human genome to discover new inflammatory syndrome Genome gov National Human Genome Research Institute Archived from the original on 5 November 2020 Retrieved 17 November 2020 a b c d Grayson PC Patel BA Young NS 2021 VEXAS syndrome Blood 137 26 3591 3594 doi 10 1182 blood 2021011455 PMC 8462403 PMID 33971000 a b Sterling D Duncan ME Philippidou M Salisbury JR Kulasekararaj AG Basu TN 2022 VEXAS syndrome vacuoles E1 enzyme X linked autoinflammatory somatic for the dermatologist Journal of the American Academy of Dermatology doi 10 1016 j jaad 2022 01 042 PMID 35121074 S2CID 246498890 a b Beck David B Ferrada Marcela A Sikora Keith A Ombrello Amanda K Collins Jason C Pei Wuhong et al 27 October 2020 Somatic Mutations in UBA1 and Severe Adult Onset Autoinflammatory Disease New England Journal of Medicine 383 27 2628 2638 doi 10 1056 NEJMoa2026834 PMC 7847551 PMID 33108101 Azvolinsky Anna February 2022 The Vexing VEXAS Syndrome ASH Clinical News Retrieved 18 July 2022 Levy Lahad Ephrat King Mary Claire 27 October 2020 Hiding in Plain Sight Somatic Mutation in Human Disease New England Journal of Medicine 383 27 2680 2682 doi 10 1056 NEJMe2030754 PMID 33108100 S2CID 225083761 Hasserjian Robert P 7 January 2022 This Year s Best in Hematology Diagnosis A New Disease Is Discovered The Hematologist 19 1 doi 10 1182 hem V19 1 2022117 ISSN 1551 8779 A Phase II Study of Allogeneic Hematopoietic Stem Cell Transplant for Subjects With VEXAS Vacuoles E1 Enzyme X linked Autoinflammatory Somatic Syndrome clinicaltrials gov 14 July 2022 Retrieved 18 July 2022 Relapsing Polychondritis Foundation 31 March 2022 The Relapsing Polychondritis Foundation Invests in the Next Phase of VEXAS Research polychondritis org Retrieved 18 July 2022 Bammert David 22 June 2022 The Relapsing Polychondritis Foundation Invests in Potentially Groundbreaking Collaborative Research Relapsing Polychondritis Relapsing Polychondritis Foundation Retrieved 19 July 2022 a href Template Cite web html title Template Cite web cite web a CS1 maint date and year link Beck David B Werner Achim Kastner Daniel L Aksentijevich Ivona 2022 05 06 Disorders of ubiquitylation unchained inflammation Nature Reviews Rheumatology 18 8 435 447 doi 10 1038 s41584 022 00778 4 ISSN 1759 4804 PMC 9075716 PMID 35523963 Research davidbecklab org Daivd B Beck Laboratory 1 July 2022 Retrieved 19 July 2022 External links EditOnline Mendelian Inheritance in Man OMIM VEXAS syndrome VEXAS 301054 Retrieved from https en wikipedia org w index php title VEXAS syndrome amp oldid 1120329348, wikipedia, wiki, book, books, library,

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