Higher risk profile among patients with TET2-mutated giant cell arteritis: a cluster analysis
Alexis F Guedon1,2, Asmaa Ouafdi2, Nabil Belfeki3
1Institut Pierre Louis d'Epidémiologie et de Santé Publique, Sorbonne Université, Institut National de la Santé et de la Recherche Médicale, Paris, France guedonalexis@gmail.com.
Insights
Clonal hematopoiesis (CH) is common in giant cell arteritis (GCA) but not significantly different from controls. Specific genetic mutations like TET2 and JAK2 identify a high-risk group in GCA patients.
Area of Science:
- Hematology
- Immunology
- Genetics
Background:
- Clonal hematopoiesis (CH) is the presence of somatic mutations in hematopoietic stem cells.
- Giant cell arteritis (GCA) is a large-vessel vasculitis with potential links to inflammatory and autoimmune processes.
Purpose of the Study:
- To determine the prevalence of CH in patients with GCA compared to controls and other autoimmune diseases (AIDs).
- To identify clinical and genetic factors associated with CH in GCA and their impact on disease outcomes.
Main Methods:
- Prospective observational study including 49 GCA patients, 48 patients with other AIDs, and 27 controls.
- Next-generation sequencing was employed to detect CH in all participants.
Main Results:
- CH was detected in 55.1% of GCA patients, 59.3% of controls, and 18.8% of other AID patients.
- No significant difference in CH prevalence was observed between GCA patients and controls or other AIDs after adjusting for age and sex.
- Cluster analysis identified two groups within GCA patients; one group with higher TET2 and JAK2 variants showed a worse prognosis.
Conclusions:
- CH is prevalent in GCA but not significantly different from controls or other AIDs.
- Specific genetic profiles (TET2, JAK2 mutations) are linked to a high-risk subgroup within the GCA cohort.
- Detecting CH in GCA patients may aid in risk stratification and guide future treatment strategies.
Objective:
We aimed to assess the prevalence of clonal haematopoiesis (CH) in patients with giant cell arteritis (GCA) compared with controls and individuals with other autoimmune diseases (AIDs) and to identify high-risk clinical/genetic profiles that could influence disease outcomes.
Methods:
In a prospective observational study at three hospitals, we included 49 patients diagnosed with GCA, 48 patients with other AIDs and 27 control participants. We used next-generation sequencing to detect clonal haematopoiesis (CH) among them.
Results:
CH was detected in 55.1% of patients with GCA, 59.3% of controls and 18.8% of patients with other AIDs. The most commonly mutated genes in GCA and control groups were DNMT3A and TET2. No significant differences in CH prevalence were found between patients with GCA and controls or other AID when adjusted for age and sex. Cluster analysis revealed two distinct groups within the patients with GCA, one of which displayed a higher prevalence of TET2 and JAK2 variants, and was associated with worse prognosis.
Conclusions:
CH is prevalent among patients with GCA but does not differ significantly from controls or other autoimmune conditions. However, specific genetic profiles, particularly mutations in TET2 and JAK2, are associated with a higher risk cluster within the GCA cohort. This observation highlights the interest of detecting CH in patients with GCA in both routine practice and clinical trials for better risk stratification. Further prospective studies are needed to determine if management tailored to the genetic profile would improve outcomes.
