A specific elastin fragment (ELP-3) as a potential serological biomarker to distinguish fibrotic from non-fibrotic hypersensitivity pneumonitis

<bold>Background:</bold> Hypersensitivity pneumonitis (HP) is defined by an exaggerated immune response that may develop into pulmonary fibrosis, often hard to distinguish from idiopathic pulmonary fibrosis (IPF). Elastin is a structural lung protein susceptible to degradation by activated neutrophils via proteinase-3. This process releases elastin fragments (ELP-3) into circulation that can be quantified by the NordicELP-3^TM assay. This study aimed to evaluate ELP-3 in HP and compare it with healthy, IPF and chronic obstructive pulmonary disease (COPD). <bold>Methods:</bold> Serum ELP-3 levels were assessed by the nordicELP-3^TM immunoassay in healthy controls (n=74), HP (n=43), COPD (n=22) and IPF (n=30) patients. HP was classified as fibrotic (n=19) or non-fibrotic (n=17). Serum ELP-3 was compared in these groups along with clinical parameters: lung function, C-reactive protein (CRP) and immune cell counts. Data were analyzed with the Mann-Whitney test, Kruskal-Wallis test, or Spearman correlation. <bold>Results:</bold> Serum ELP-3 was elevated in HP (median 10.82 μg/mL), IPF (6.16 μg/mL) and COPD (8.64 μg/mL) compared to healthy controls (4.47 μg/mL; all groups p<0.0001), and in HP compared to IPF (p<0.0001). Forced vital capacity (FVC) and serum ELP-3 were higher in non-fibrotic relative to fibrotic HP (median FVC 102% vs. 85, p=0.038; ELP-3 11.30 vs. 10.35 μg/mL; p=0.023). No correlation was found between serum ELP-3 and FVC. <bold>Conclusions:</bold> Serum ELP-3 was elevated in various lung diseases and distinguished non-fibrotic from fibrotic HP, unlike CRP and immune cell counts. As a non-invasive test, ELP-3 may offer additional clinical insights beyond standard inflammation markers.