C71-21 Emerging Biomarkers in Interstitial Lung Disease and Their Role in Identifying Progressive Phenotypes

Rationale Despite advances in therapies, the ability to identify patients affected by interstitial lung diseases (ILDs) at risk for disease progression, remains limited. Matrix metalloproteinase-7 (MMP7), expressed by aberrant basaloid cells in idiopathic pulmonary fibrosis (IPF), is a marker of pathological epithelial transformation. High serum levels correlate with disease severity, accelerated lung function decline, and increased mortality risk. C-C motif chemokine ligand 18 (CCL18), constitutively released by alveolar macrophages, sustains collagen deposition in IPF. Serum concentrations above 150 ng/ml confer an eightfold increased risk of death, while longitudinal changes closely mirror disease trajectory. Circulating biomarkers have shown clinical promise in IPF, but their role across the broader ILD spectrum remains incompletely defined. This study evaluated the diagnostic and prognostic performance of serum MMP7 and CCL18 in a heterogeneous ILD cohort and outlines the next-generation biomarker strategy integrating neoepitope profiling. Methods Serum concentrations of MMP7 and CCL18 were quantified by ELISA in patients with fibrotic and non-fibrotic ILDs, including IPF, non-IPF progressive pulmonary fibrosis (PPF), and COVID-related ILDs. Data distribution and normality were assessed, followed by comparison and correlation tests. Disease progression was defined according to both ATS and INBUILD criteria. Correlations with pulmonary function, symptom severity, and the Gender-Age-Physiology (GAP) index were analyzed. Results No significant differences in MMP7 concentrations (Figure 1) were found among diagnostic groups or progression categories (all p > 0.05), and its correlation with the GAP index was low (Spearman r = 0.21, p = 0.07). Conversely, CCL18 levels demonstrated significant associations with disease progression by ATS (p = 0.045) and INBUILD (p = 0.041) criteria and correlated with baseline pulmonary function impairment (p = 0.044) and the GAP index (r = +0.33, p = 0.003). CCL18 concentrations (Figure 2and 2b), however, did not discriminate between IPF and non-IPF phenotypes or between radiological/histological patterns. Conclusions Our findings confirm CCL18 as a reproducible biomarker of disease activity and progression across fibrosing ILDs, whereas MMP7, despite its strong biological rationale, did not achieve predictive significance in this heterogeneous cohort. Recognizing the limitations of ELISA-based single-analyte assays, we now aim to implement the Nordic Bioscience Protein Fingerprint Technology to quantify specific extracellular neoepitopes (C3M, PRO-C3, PRO-C6, C4Ma3, PRO-C4, PRO-C8, C6M, and VICM) in serum samples. This next-generation approach will enable a multidimensional assessment of molecular signatures of fibrogenesis, epithelial damage, macrophage activity, and vascular remodeling, and will ultimately advance biomarker-driven strategies for patient stratification and clinical monitoring. This abstract is funded by: Astrazeneca