Hyaluronan in the pathogenesis of lung fibrosis associated to autoimmune Pulmonary Alveolar Proteinosis (aPAP)

<bold>Rationale.</bold> Pulmonary fibrosis is a rare but well-recognized event which may occurs in a minority of patients with aPAP. The accumulation of intra-alveolar material may alter local cytokine expression, promoting proinflammatory and profibrotic pathways however much remains to be known regarding the pathogenesis of this complication. <bold>Aim.</bold> We aimed to investigate serum biomarkers able to serve as prognostic factor for the development of lung fibrosis in aPAP patients (pts). <bold>Methods.</bold> We perfomed the ELF™ test (Siemens), a multivariate index assay providing 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 17 aPAP pts, collected at diagnosis. <bold>Results.</bold> We compared 7 aPAP pts who show lung fibrosis evidence on chest HRTC (PAPFIB) with 10 pts (PAP) who did not developed lung fibrosis within at least 9 years from aPAP diagnosis. We found that both PAPFIB and PAP show a positive association with the risk of fibrosis (mean ELF score 9.3+0.71 vs 8.5+0.48 respectively, positive score>7.7), with a significant increase in PAPFIB group (p=0.016). In particular, mean HA levels were found to be significantly elevated in PAPFIB compared to PAP (58.42+47.3 vs 22.53 +9.57 ng/mL, p=0.032, positive range> 34.6+ 8.8). <bold>Conclusion.</bold> Although within a limited sample size, our preliminary results seem to indicate that a robust HA production in the lungs and peripheral tissues contributes to the chronic inflammatory and micro injury to the alveolar epithelium and describe the utility of HA as a prognostic biomarker of fibrosis associated to aPAP.