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

The detection of somatic mutations in genes of myeloid cells in asymptomatic patients - defining clonal hematopoiesis of indeterminate potential (CHIP) - predisposes to cardiovascular events (CVE) in the general population. We aimed to determine whether CHIP was associated with CVE in SLE patients.The study is an ancillary study of the randomized, double-blind, placebo-controlled, multicenter trial PLUS study conducted from June 2007 through August 2010 at 37 centers in France involving 573 SLE patients. The search for somatic mutations by high-throughput sequencing of 53 genes involved in clonal hematopoiesis was performed on genomic DNA collected at PLUS inclusion. The CHIP prevalence was assessed in SLE and in a retrospective cohort of 479 patients free of hematological malignancy. The primary outcome was the incident CVE in SLE.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 was associated with age, age at SLE diagnosis and a lower frequency of antiphospholipid antibodies. CHIP occurred more than 20-years earlier (p < 0·00001) in SLE than in controls. The detection of CHIP at inclusion was not associated with the occurrence of CVE during follow up (HR = 0·42 (0·06 - 3·21), p = 0·406).The prevalence of CHIP is high in SLE with respect to age but was not associated with incident CVE.ClinicalTrials.gov, https://clinicaltrials.gov, NCT05146414.