Francesco Del Galdo

Background Systemic sclerosis (SSc) is a heterogeneous disease, characterized by variable tissue and vascular fibrosis in the context of autoimmune activation. The C‐C Motif Chemokine Ligand 24 (CCL24 or Eotaxin2) has been shown to promote microangiopathic, pro‐inflammatory, and pro‐fibrotic processes in preclinical models of SSc. Here we study serum CCL24 levels in a real‐life cohort of SSc patients, to determine its distribution across disease features and its value in predicting disease progression and related mortality. Methods Serum CCL24 was assessed in an observational cohort of consecutively enrolled SSc patients. A high CCL24 cut‐off was defined based on its distribution in a matched cohort of healthy controls. Disease progression and mortality were analysed from the date of serum assessment. Results Two‐hundred‐thirteen consecutively enrolled patients with SSc were included in this analysis. Median disease duration was 6 years (IQR 3‐14), 28.6% of patients presented with interstitial lung disease (ILD), 46.9% had digital ulcers and 25.3% showed high CCL24 serum concentration. High CCL24 patients were more frequently male, with anti‐SCL‐70 positive, with a diagnosis of ILD and synovitis (p<0.05 for all). Notably, high CCL24 patients had lower DLco and higher prevalence of digital ulcers, telangiectasias, and calcinosis (p<0.05 for all). In a longitudinal setting, high CCL24 was associated with greater lung function decline and with higher disease‐related mortality. Conclusion Serum CCL24 is a biomarker of disease severity across fibrotic and vascular disease manifestations. These data support the development of therapies targeting CCL24 as a novel comprehensive therapeutic target in SSc.