Clonal haematopoiesis of indeterminate potential and cardiovascular events in systemic lupus erythematosus (HEMATOPLUS study). (17th February 2022)

• Record Type: Journal Article
• Authors: David, Clémence; Duployez, Nicolas; Eloy, Philippine; Belhadi, Drifa; Chezel, Julie; Guern, Véronique Le; Laouénan, Cédric; Fenwarth, Laurène; Rouzaud, Diane; Mathian, Alexis ; de Almeida Chaves, Sébastien; Duhaut, Pierre; Fain, Olivier; Galicier, Lionel ; Ghillani-Dalbin, Pascale; Kahn, Jean Emmanuel; Morel, Nathalie; Perard, Laurent ; Pha, Micheline; Sarrot-Reynauld, Francoise; Aumaitre, Olivier; Chasset, François ; Limal, Nicolas; Desmurs-Clavel, Helene; Ackermann, Felix; Amoura, Zahir ; Papo, Thomas; Preudhomme, Claude; Costedoat-Chalumeau, Nathalie; Sacre, Karim
• Is Part Of: Rheumatology. Volume 61:Number 11(2022)
• Page Start: 4355
• Page End: 4363
• Publication Date: 2022-02-17
• Subjects: clonal haematopoiesis of indeterminate potential -- lupus -- cardiovascular events; Rheumatism -- Periodicals; Rheumatology -- Periodicals; 616.723005
• DOI: 10.1093/rheumatology/keac108
• Languages: English
• ISSNs: 1462-0324

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.