PMID- 38049983
OWN - NLM
STAT- MEDLINE
DCOM- 20240314
LR  - 20240316
IS  - 1468-2060 (Electronic)
IS  - 0003-4967 (Print)
IS  - 0003-4967 (Linking)
VI  - 83
IP  - 4
DP  - 2024 Mar 12
TI  - Clonal haematopoiesis across the age spectrum of vasculitis patients with 
      Takayasu's arteritis, ANCA-associated vasculitis and giant cell arteritis.
PG  - 508-517
LID - 10.1136/ard-2023-224933 [doi]
AB  - OBJECTIVES: Ageing and inflammation are associated with clonal haematopoiesis 
      (CH), the emergence of somatic mutations in haematopoietic cells. This study 
      details CH in patients with systemic vasculitis in association with clinical, 
      haematological and immunological parameters. METHODS: Patients with three forms 
      of vasculitis were screened for CH in peripheral blood by error-corrected 
      sequencing. Relative contributions of age and vasculitis on CH prevalence were 
      calculated using multivariable logistic regression. Clonal hierarchies were 
      assessed by proteogenomic single-cell DNA sequencing, and functional experiments 
      were performed in association with CH status. RESULTS: Patients with Takayasu's 
      arteritis (TAK; n=70; mean age=33.2 years), antineutrophil cytoplasmic 
      antibody-associated vasculitis (AAV; n=47; mean age=55.3 years) and giant cell 
      arteritis (GCA; n=59; mean age=71.2 years) were studied. CH, most commonly in 
      DNMT3A and TET2, was detected in 34% (60/176) of patients versus 18% (28/151) of 
      age-matched controls (p<0.01). Prevalence of CH was independently associated with 
      age (standardised B=0.96, p<0.01) and vasculitis (standardised B=0.46, p<0.01), 
      occurring in 61%, 32% and 13% of patients with GCA, AAV and TAK, respectively. 
      Both branched and linear clonal trajectories showed myeloid-lineage bias, and CH 
      was associated with markers of cellular activation. In GCA, mutations were 
      detected in temporal artery biopsies, and clinical relapse correlated with CH in 
      a dose-dependent relationship with clone size. CONCLUSIONS: Age was more strongly 
      associated with CH prevalence than inflammation in systemic vasculitis. Clonal 
      profile was dominated by DNMT3A mutations which were associated with relapse in 
      GCA. CH is not likely a primary causal factor in systemic vasculitis but may 
      contribute to inflammation.
CI  - (c) Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and 
      permissions. Published by BMJ.
FAU - Gutierrez-Rodrigues, Fernanda
AU  - Gutierrez-Rodrigues F
AD  - Hematology Branch, National Heart Lung and Blood Institute Division of Intramural 
      Research, Bethesda, Maryland, USA.
FAU - Wells, Kristina V
AU  - Wells KV
AD  - National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, 
      Maryland, USA.
FAU - Jones, Adrianna I
AU  - Jones AI
AD  - National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, 
      Maryland, USA.
FAU - Hironaka, Dalton
AU  - Hironaka D
AD  - Hematology Branch, National Heart Lung and Blood Institute Division of Intramural 
      Research, Bethesda, Maryland, USA.
FAU - Rankin, Cameron
AU  - Rankin C
AD  - National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, 
      Maryland, USA.
FAU - Gadina, Massimo
AU  - Gadina M
AUID- ORCID: 0000-0001-9084-6736
AD  - National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, 
      Maryland, USA.
FAU - Sikora, Keith A
AU  - Sikora KA
AD  - National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, 
      Maryland, USA.
FAU - Alemu, Lemlem
AU  - Alemu L
AD  - Hematology Branch, National Heart Lung and Blood Institute Division of Intramural 
      Research, Bethesda, Maryland, USA.
FAU - Calado, Rodrigo T
AU  - Calado RT
AD  - Medical Imaging, Hematology, and Oncology, University of Sao Paulo, Sao Paulo, 
      Brazil.
FAU - Quinn, Kaitlin A
AU  - Quinn KA
AUID- ORCID: 0000-0002-5794-194X
AD  - National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, 
      Maryland, USA.
FAU - Patel, Bhavisha
AU  - Patel B
AD  - Hematology Branch, National Heart Lung and Blood Institute Division of Intramural 
      Research, Bethesda, Maryland, USA.
FAU - Young, Neal S
AU  - Young NS
AD  - Hematology Branch, National Heart Lung and Blood Institute Division of Intramural 
      Research, Bethesda, Maryland, USA.
FAU - Grayson, Peter C
AU  - Grayson PC
AUID- ORCID: 0000-0002-8269-9438
AD  - National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, 
      Maryland, USA peter.grayson@nih.gov.
LA  - eng
GR  - Z99 AR999999/ImNIH/Intramural NIH HHS/United States
PT  - Journal Article
DEP - 20240312
PL  - England
TA  - Ann Rheum Dis
JT  - Annals of the rheumatic diseases
JID - 0372355
SB  - IM
MH  - Humans
MH  - Adult
MH  - Middle Aged
MH  - Aged
MH  - *Giant Cell Arteritis/epidemiology
MH  - *Takayasu Arteritis/epidemiology
MH  - Clonal Hematopoiesis
MH  - *Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
MH  - Inflammation
MH  - Recurrence
PMC - PMC10939924
MID - NIHMS1947613
OTO - NOTNLM
OT  - Giant Cell Arteritis
OT  - Polymorphism, Genetic
OT  - Vasculitis
COIS- Competing interests: None declared.
EDAT- 2023/12/05 12:43
MHDA- 2024/03/14 06:46
PMCR- 2025/03/12
CRDT- 2023/12/05 00:53
PHST- 2023/08/29 00:00 [received]
PHST- 2023/11/14 00:00 [accepted]
PHST- 2025/03/12 00:00 [pmc-release]
PHST- 2024/03/14 06:46 [medline]
PHST- 2023/12/05 12:43 [pubmed]
PHST- 2023/12/05 00:53 [entrez]
AID - ard-2023-224933 [pii]
AID - 10.1136/ard-2023-224933 [doi]
PST - epublish
SO  - Ann Rheum Dis. 2024 Mar 12;83(4):508-517. doi: 10.1136/ard-2023-224933.