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Serum CCL24 as a biomarker of fibrotic and vascular disease severity in Systemic Sclerosis.
Arthritis Care & Research 2024 April 9
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.
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.
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