Association of Somatic TET2 Mutations With Giant Cell Arteritis

Michelle L. Robinette, Lachelle D. Weeks, Ryan J. Kramer, Mridul Agrawal, Christopher J. Gibson, Zhi Yu, Aswin Sekar, Arnav Mehta, Abhishek Niroula, Jared T. Brown, Gregory C. McDermott, Edith R. Reshef, Jonathan E. Lu, Victor D. Liou, Carolina A. Chiou, Pradeep Natarajan, Suzanne K. Freitag, Deepak A. Rao, Benjamin L. Ebert

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: Giant cell arteritis (GCA) is an age-related vasculitis. Prior studies have identified an association between GCA and hematologic malignancies (HMs). How the presence of somatic mutations that drive the development of HMs, or clonal hematopoiesis (CH), may influence clinical outcomes in GCA is not well understood. Methods: To examine an association between CH and GCA, we analyzed sequenced exomes of 470,960 UK Biobank (UKB) participants for the presence of CH and used multivariable Cox regression. To examine the clinical phenotype of GCA in patients with and without somatic mutations across the spectrum of CH to HM, we performed targeted sequencing of blood samples and electronic health record review on 114 patients with GCA seen at our institution. We then examined associations between specific clonal mutations and GCA disease manifestations. Results: UKB participants with CH had a 1.48-fold increased risk of incident GCA compared to UKB participants without CH. GCA risk was highest among individuals with cytopenia (hazard ratio [HR] 2.98, P = 0.00178) and with TET2 mutation (HR 2.02, P = 0.00116). Mutations were detected in 27.2% of our institutional GCA cohort, three of whom had HM at GCA diagnosis. TET2 mutations were associated with vision loss in patients with GCA (odds ratio 4.33, P = 0.047). Conclusions: CH increases risk for development of GCA in a genotype-specific manner, with the greatest risk being conferred by the presence of mutations in TET2. Somatic TET2 mutations likewise increase the risk of GCA-associated vision loss. Integration of somatic genetic testing in GCA diagnostics may be warranted in the future.

Original languageEnglish
Pages (from-to)438-443
Number of pages6
JournalArthritis and Rheumatology
Volume76
Issue number3
Early online date2023
DOIs
Publication statusPublished - 2024 Mar

Subject classification (UKÄ)

  • Rheumatology and Autoimmunity

Fingerprint

Dive into the research topics of 'Association of Somatic TET2 Mutations With Giant Cell Arteritis'. Together they form a unique fingerprint.

Cite this