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

Clémence David 1, 2 Nicolas Duployez 3 Philippine Eloy 4, 5 Drifa Belhadi 2 Julie Chezel 1, 2 Véronique Le Guern 6, 7 Cédric Laouénan 2 Laurène Fenwarth 3, 8 Diane Rouzaud 1, 2 Alexis Mathian 9 Sébastien de Almeida Chaves 10 Pierre Duhaut 11, 12 Olivier Fain 13 Lionel Galicier 14 Pascale Ghillani-Dalbin 15 Jean Emmanuel Kahn 16, 17 Nathalie Morel 6, 7 Laurent Perard 18 Micheline Pha 9 Francoise Sarrot-Reynauld 19 Olivier Aumaitre François Chasset Nicolas Limal Helene Desmurs-Clavel Felix Ackermann Zahir Amoura Thomas Papo Claude Preudhomme Nathalie Costedoat-Chalumeau Karim Sacre 
Abstract : 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.
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https://hal-u-picardie.archives-ouvertes.fr/hal-03856560
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Soumis le : mercredi 16 novembre 2022 - 18:20:51
Dernière modification le : mardi 22 novembre 2022 - 14:26:16

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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⟩

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