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Association of Somatic TET2 Mutations With Giant Cell Arteritis.
Robinette, Michelle L; Weeks, Lachelle D; Kramer, Ryan J; Agrawal, Mridul; Gibson, Christopher J; Yu, Zhi; Sekar, Aswin; Mehta, Arnav; Niroula, Abhishek; Brown, Jared T; McDermott, Gregory C; Reshef, Edith R; Lu, Jonathan E; Liou, Victor D; Chiou, Carolina A; Natarajan, Pradeep; Freitag, Suzanne K; Rao, Deepak A; Ebert, Benjamin L.
Affiliation
  • Robinette ML; Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, Massachusetts.
  • Weeks LD; Dana-Farber Cancer Institute and Center for Leukemia and Center for Early Detection and Interception of Blood Cancers, Boston, Massachusetts.
  • Kramer RJ; Dana-Farber Cancer Institute, Boston, Massachusetts, and Duke University School of Medicine, Durham, North Carolina.
  • Agrawal M; Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Gibson CJ; Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Yu Z; The Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, and Cardiovascular Research Center, Massachusetts General Hospital, Boston.
  • Sekar A; Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Mehta A; Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston.
  • Niroula A; Dana-Farber Cancer Institute, Boston, Massachusetts, The Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, and Lund University, Lund, Sweden.
  • Brown JT; Dana-Farber Cancer Institute, Boston, Massachusetts.
  • McDermott GC; Brigham and Women's Hospital, Boston, Massachusetts.
  • Reshef ER; Massachusetts Eye and Ear Infirmary, Harvard Medical School and Boston Children's Hospital, Boston, Massachusetts.
  • Lu JE; Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts.
  • Liou VD; Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts.
  • Chiou CA; Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts.
  • Natarajan P; The Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, and Cardiovascular Research Center, Massachusetts General Hospital, Boston.
  • Freitag SK; Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts.
  • Rao DA; Brigham and Women's Hospital, Boston, Massachusetts.
  • Ebert BL; Dana-Farber Cancer Institute, Boston, The Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, and Howard Hughes Medical Institute, Boston, Massachusetts.
Arthritis Rheumatol ; 76(3): 438-443, 2024 Mar.
Article in En | MEDLINE | ID: mdl-37909388
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.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Giant Cell Arteritis / Dioxygenases Limits: Humans Language: En Journal: Arthritis Rheumatol Year: 2024 Document type: Article

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Giant Cell Arteritis / Dioxygenases Limits: Humans Language: En Journal: Arthritis Rheumatol Year: 2024 Document type: Article