Prevalence and clinical associations of age-related clonal hematopoiesis in systemic sclerosis

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ID: 338747
2026
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Abstract
OBJECTIVES: Systemic sclerosis (SSc) is an autoimmune disease involving both innate and adaptive immunity, characterized by progressive organ fibrosis. Age-related clonal hematopoiesis (ARCH) results from somatic mutations in hematopoietic progenitors and is increasingly implicated in inflammation and autoimmunity. We aimed to assess the prevalence of ARCH in patients with SSc and its association with disease characteristics. METHODS: Targeted myeloid next-generation sequencing (NGS) was performed in 196 patients with SSc and 392 age- and gender-matched individuals without SSc and referred for NGS without a final diagnosis myelodysplastic syndrome. Variants with variant allele frequency (VAF) ≥0.8% were considered for ARCH analysis. Clonal hematopoiesis of indeterminate potential (CHIP) was defined as ARCH with a VAF ≥2%. RESULTS: The prevalence of ARCH and CHIP was similar between SSc patients and the control group: 32.7% vs. 37.2% (p = 0.25) and 23.5% vs. 28.8% (p = 0.15), respectively. Among patients with SSc, ARCH was associated with higher NT-proBNP levels and higher prevalence of progressive interstitial lung disease (ILD) (39.1% versus 15.7%, p = 0.026), pulmonary hypertension (23.4% vs. 11.4%, p = 0.028), valvular heart disease (23.4% vs. 11.4%, p = 0.028), anti-centromere antibodies (65.1% versus 49.6%, p = 0.043) in our cohort. After adjustment to age and gender, only NT-proBNP levels remain significantly higher in SSc patients with ARCH. These associations were not observed when restricting the analysis to CHIP except for valvular heart disease (26.1% vs. 11.4%, p = 0.019) and higher NT proBNP levels. CONCLUSION: The prevalence of ARCH and CHIP was 32.7% and 23.5% respectively in our cohort of patients with SSc Presence of ARCH was associated with more severe pulmonary involvement, a higher frequency of pulmonary hypertension, valvular heart disease and anti-centromere antibodies. After adjustement to age and sex, ARCH was associate with a higher NT-pro BNP levels.
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Authors Hélène Maachi, Laurène Fenwarth, Nicolas Duployez, Camille Ternynck, A Collet, Sylvain Dubucquoi, Louis Terriou, Sébastien Sanges, Vincent Sobanski, Eric Hachulla, David Launay
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Journal international journal of rheumatology
Year 2026
DOI
10.1093/rheumatology/keag600
URL
https://doi.org/10.1093/rheumatology/keag600
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