Clonal haematopoiesis of indeterminate potential and cardiovascular events in systemic lupus erythematosus (HEMATOPLUS study) - Université de Picardie Jules Verne Accéder directement au contenu
Article Dans Une Revue Rheumatology Année : 2022

Clonal haematopoiesis of indeterminate potential and cardiovascular events in systemic lupus erythematosus (HEMATOPLUS study)

Alexis Mathian
Olivier Fain

Résumé

Abstract Objective The detection of somatic mutations among the genes of myeloid cells in asymptomatic patients—defining clonal haematopoiesis of indeterminate potential (CHIP)—is associated with a predisposition to cardiovascular events (CVEs) in the general population. We aimed to determine whether CHIP was associated with CVEs in SLE patients. Methods The study is an ancillary study of the randomized, double-blind, placebo-controlled, multicentre PLUS trial conducted from June 2007 through August 2010 at 37 centres in France, involving 573 SLE patients. The search for somatic mutations by high-throughput sequencing of 53 genes involved in clonal haematopoiesis was performed on genomic DNA collected at PLUS inclusion. CHIP prevalence was assessed in SLE and in a retrospective cohort of 479 patients free of haematological malignancy. The primary outcome was an incident CVE in SLE. Results Screening for CHIP was performed in 438 SLE patients [38 (29–47) years, 91.8% female]. Overall, 63 somatic mutations were identified in 47 patients, defining a CHIP prevalence of 10.7% in SLE. Most SLE patients (78.7%) carried a single mutation. Most variants (62.5%) were located in the DNMT3A gene. CHIP frequency was related to age and to age at SLE diagnosis, and was associated with a lower frequency of aPLs. CHIP occurred >20 years earlier (P < 0.00001) in SLE than in controls. The detection of CHIP at inclusion was not found to be associated with occurrence of CVEs during follow-up [HR = 0.42 (0.06–3.21), P = 0.406]. Conclusion The prevalence of CHIP is relatively high in SLE for a given age, but was not found to be associated with incident CVEs. Trial registration ClinicalTrials.gov, https://clinicaltrials.gov, NCT05146414.
Fichier principal
Vignette du fichier
Sacre CHIP SLE Rheumatology HAL.pdf (595.56 Ko) Télécharger le fichier
Origine Fichiers produits par l'(les) auteur(s)

Dates et versions

hal-03856560 , version 1 (16-01-2023)

Identifiants

Citer

Clémence David, Nicolas Duployez, Philippine Eloy, Drifa Belhadi, Julie Chezel, et al.. Clonal haematopoiesis of indeterminate potential and cardiovascular events in systemic lupus erythematosus (HEMATOPLUS study). Rheumatology, 2022, 61 (11), pp.4355-4363. ⟨10.1093/rheumatology/keac108⟩. ⟨hal-03856560⟩
129 Consultations
119 Téléchargements

Altmetric

Partager

Gmail Mastodon Facebook X LinkedIn More