Somatic mutations in rheumatological diseases: VEXAS syndrome and beyond

Sikora K. A., Wells K. V., Bolek E. C., Jones A. I., Grayson P. C.

Rheumatology (Oxford, England), vol.61, no.8, pp.3149-3160, 2022 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Review
  • Volume: 61 Issue: 8
  • Publication Date: 2022
  • Doi Number: 10.1093/rheumatology/keab868
  • Journal Name: Rheumatology (Oxford, England)
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CINAHL, EMBASE, International Pharmaceutical Abstracts, MEDLINE
  • Page Numbers: pp.3149-3160
  • Keywords: VEXAS syndrome, somatic mutations, clonal haematopoiesis, autoinflammatory disease, autoimmune disease
  • Hacettepe University Affiliated: Yes


Published by Oxford University Press on behalf of the British Society for Rheumatology 2021. This work is written by a US Government employee and is in the public domain in the US.Discovery of the VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome demonstrates that somatic mutations in haematological precursor cells can cause adult-onset, complex inflammatory disease. Unlike germline mutations, somatic mutations occur throughout the lifespan, are restricted to specific tissue types, and may play a causal role in non-heritable rheumatological diseases, especially conditions that start in later life. Improvements in sequencing technology have enabled researchers and clinicians to detect somatic mutations in various tissue types, especially blood. Understanding the relationships between cell-specific acquired mutations and inflammation is likely to yield key insights into causal factors that underlie many rheumatological diseases. The objective of this review is to detail how somatic mutations are likely to be relevant to clinicians who care for patients with rheumatological diseases, with particular focus on the pathogenetic mechanisms of the VEXAS syndrome.