Research Article: Hyaluronan in the pathogenesis of lung fibrosis associated to autoimmune pulmonary alveolar proteinosis (aPAP)
Abstract:
Pulmonary fibrosis is a rare event occurring in patients with autoimmune Pulmonary Alveolar Proteinosis (aPAP). The accumulation of intra-alveolar material may promote proinflammatory and profibrotic pathways.
To investigate serum biomarkers as prognostic factor of lung fibrosis in aPAP.
We performed the ELF™ test (Siemens), which provides a score of fibrosis based on quantitative measurements of hyaluronic acid (HA), amino-terminal propeptide of type III procollagen (PIIINP), and tissue inhibitor of metalloproteinase 1 (TIMP-1) from serum of 21 aPAP patients, collected at diagnosis.
In this retrospective cohort study, we analyzed the serum samples collected at aPAP diagnosis from10 patients (PAP-FIB) showing lung fibrosis evidence on chest HRTC and 11 patients (PAP) who did not develop lung fibrosis within at least 9 years from aPAP diagnosis. Both PAP-FIB and PAP groups exhibited ELF scores above the risk threshold (>7.7), with significantly higher values in PAP-FIB (mean ELF score: 9.19 ± 0.75 vs. 8.52 ± 0.46, p = 0.02). Mean HA levels were also significantly elevated in PAP-FIB compared to PAP (55.61 ± 42.01 ng/mL vs. 22.83 ± 9.13 ng/mL, p = 0.02). After adjusting for differences in DLCO, HA remained a marginally significant predictor of fibrosis ( p = 0.05) while the difference in ELF scores between the two groups was no longer statistically significant. ROC analysis demonstrated an AUROC of 0.8, with an optimal cut-off of 9 (sensitivity 70%, specificity 91%) for ELF and an AUROC of 0.8, with a cut-off of 41 ng/mL (100% specificity and 60% sensitivity) for HA.
Our results seem to indicate that a robust HA production contributes to the chronic inflammatory and micro-injury to the alveolar epithelium. The high specificity of HA highlights its utility as a prognostic biomarker of aPAP-associated fibrosis.
Introduction:
Pulmonary fibrosis is a rare event occurring in patients with autoimmune Pulmonary Alveolar Proteinosis (aPAP). The accumulation of intra-alveolar material may promote proinflammatory and profibrotic pathways.
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