Higher risk profile among patients with TET2-mutated giant cell arteritis: a cluster analysis
Arsène Mekinian,
Nabil Belfeki,
Olivier Fain,
Jean-Yves Scoazec,
Olivier Hermine,
Julien Rossignol,
Nouha Ghriss,
Azeddine Dellal,
Olivier Espitia,
Alexis F Guedon,
Christophe Marzac,
Asmaa Ouafdi,
Marc Scheen,
Fadi Haidar,
Eric Solary
Affiliations
Arsène Mekinian
Sorbonne Université Service de médecine interne, AP-HP, Hôpital Saint Antoine, Paris, France
Nabil Belfeki
Hôpital de Melun, Service de Médecine Interne, Melun, France
Olivier Fain
Sorbonne Université, APHP, Service de Médecine Interne, Hopital Saint-Antoine, Paris, Île-de-France, France
Jean-Yves Scoazec
Institut Gustave-Roussy, Villejuif, France
Olivier Hermine
CEREMAST, Paris University, Imagine Institute, INSERM U1163, Necker-Enfants Malades University Hospital, Paris, France
Julien Rossignol
Imagine Institute, Paris, France
Nouha Ghriss
Hôpital de Melun, Service de Médecine Interne, Melun, France
Azeddine Dellal
Hôpital Montfermeil, Service de Médecine Interne et Rhumatologie, Montfermeil, France
Olivier Espitia
Nantes Université, CHU Nantes, Department of Internal and Vascular Medicine, l`institut du thorax, INSERM UMR1087/CNRS UMR 6291, Team III Vascular & Pulmonary diseases, Nantes, France
Alexis F Guedon
Institut Pierre Louis d`Epidemiologie et de Sante Publique, Paris, Île-de-France, France
Christophe Marzac
Institut Gustave-Roussy, Villejuif, France
Asmaa Ouafdi
Sorbonne Université Service de médecine interne, AP-HP, Hôpital Saint Antoine, Paris, France
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.