Background: Emerging evidence have supported that the accumulation of both germline and somatic mutations contributed to the development of SLE [1–3]. Clonal hematopoiesis of indeterminate potential (CHIP) detection is linked with chronic inflammation and an elevated risk of cardiovascular events (CVEs) in the general population [4–7].

Objectives: We sought to delve into the clinical implications of CHIP, particularly its correlation with early indicators of CVEs, in patients with childhood-onset systemic lupus erythematosus (cSLE).

Methods: We conducted high-throughput sequencing of 54 genes associated with CHIP on genomic DNA obtained from 106 cSLE patients diagnosed before the age of 18. We collected and analyzed data on patients’ clinical manifestations, biomarkers of endothelial cell dysregulation, and echocardiography results.

Results: Among the 106 cSLE patients, with a median age of 20 years (IQR: 9 years), we identified a total of 15 CHIP instances across 10 genes in 16 patients (15.09%). Predominantly, mutations were situated in the ASXL1 gene (25%), followed by TET2, SETDB1, NOTCH2 and others. Patients with CHIP were older at the time of DNA sampling (24 vs. 18; p = 0.021). Additionally, patients with CHIP mutations exhibited a lower E/A ratio (1.30 vs. 1.55; p = 0.022), reduced ascending aorta velocity (0.89 vs. 1.06; p = 0.015), and thicker carotid intima-media thickness (IMT) (0.47 vs. 0.44; p = 0.015) compared to those without CHIP. No significant differences were observed between the two groups in terms of other clinical manifestations, therapeutic regimens, or laboratory data, including dyslipidemia.

Conclusion: Our study unveils a noteworthy prevalence of CHIP in cSLE patients. Compared to those without CHIP, cSLE patients with CHIP demonstrate thicker IMT, highlighting the importance of vigilant monitoring for atherosclerosis development.

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[2] Fasano S, Milone A, Nicoletti GF et al. Precision medicine in systemic lupus erythematosus. Nat Rev Rheumatol 2023;19:331-42.

[3] David C, Duployez N, Eloy P et al. Clonal haematopoiesis of indeterminate potential and cardiovascular events in systemic lupus erythematosus (HEMATOPLUS study). Rheumatology (Oxford) 2022;61:4355-63.

[4] Uddin MDM, Nguyen NQH, Yu B et al. Clonal hematopoiesis of indeterminate potential, DNA methylation, and risk for coronary artery disease. Nature Communications 2022;13.

[5] Marnell CS, Bick A, Natarajan P. Clonal hematopoiesis of indeterminate potential (CHIP): Linking somatic mutations, hematopoiesis, chronic inflammation and cardiovascular disease. J Mol Cell Cardiol 2021;161:98-105.

[6] Buscarlet M, Provost S, Zada YF et al. DNMT3A and TET2 dominate clonal hematopoiesis and demonstrate benign phenotypes and different genetic predispositions. Blood 2017;130:753-62.

[7] Pascual-Figal DA, Bayes-Genis A, Diez-Diez M et al. Clonal Hematopoiesis and Risk of Progression of Heart Failure With Reduced Left Ventricular Ejection Fraction. J Am Coll Cardiol 2021;77:1747-59.

Acknowledgements: NIL.

Disclosure of Interests: None declared.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.