Batchelor Degree in Biotechnology at University of Piemonte Orientale (UniUPO)
Master Degree in Medical and Pharmaceutical Biotechnology at Università degli Studi di Pavia
RESEARCH, TEACHING, or OTHER INTERESTS
Biotechnology, Biochemistry, Genetics and Molecular Biology
3
Scopus Publications
Scopus Publications
The dark side of pulmonary alveolar proteinosis Sara Lettieri, Francesca Mariani, Vincenzo Alfredo Marando, Elena Salvaterra, Angelo Guido Corsico, Ilaria Campo Multidisciplinary Respiratory Medicine, 2025 Background: Pulmonary alveolar proteinosis (PAP) has an unpredictable clinical course. Although usually benign, an association with pulmonary fibrosis is described in literature, with troubling therapeutic and prognostic implications. Clinical case: We report the case of a patient affected by autoimmune PAP who developed pleuro-parenchymal fibroelastosis (PPFE) after 6 years of disease and underwent bilateral lung transplantation due to end stage respiratory failure. Conclusion: Punctual descriptions of pulmonary fibrosis in PAP are still lacking and no predictors of fibrotic evolution of PAP are known. It is necessary to ensure a strict follow up in order to promptly recognize signs of fibrotic evolution and early refer patients with evolutive disease to lung transplant center. Moreover, an extended genetic analysis by targeted next-generation sequencing could provide high-resolution information that may allow the identification of susceptible patients in a pre-fibrotic stage of disease.
Hyaluronan in the pathogenesis of lung fibrosis associated to autoimmune pulmonary alveolar proteinosis (aPAP) Raffaele Gentile, Vincenzo Alfredo Marando, Francesca Mariani, Sara Lettieri, Matteo Della Zoppa, Michele Zorzetto, Laura Maria Ciardelli, Riccardo Albertini, Annalisa De Silvestri, Angelo Guido Corsico, Ilaria Campo Frontiers in Medicine, 2025 IntroductionPulmonary 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.AimTo investigate serum biomarkers as prognostic factor of lung fibrosis in aPAP.MethodsWe 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.ResultsIn 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.ConclusionOur 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.
Pathogenesis-driven treatment of primary pulmonary alveolar proteinosis Sara Lettieri, Francesco Bonella, Vincenzo Alfredo Marando, Alessandro N Franciosi, Angelo Guido Corsico, Ilaria Campo European Respiratory Review, 2024 Pulmonary alveolar proteinosis (PAP) is a syndrome that results from the accumulation of lipoproteinaceous material in the alveolar space. According to the underlying pathogenetic mechanisms, three different forms have been identified, namely primary, secondary and congenital. Primary PAP is caused by disruption of granulocyte−macrophage colony-stimulating factor (GM-CSF) signalling due to the presence of neutralising autoantibodies (autoimmune PAP) or GM-CSF receptor genetic defects (hereditary PAP), which results in dysfunctional alveolar macrophages with reduced phagocytic clearance of particles, cholesterol and surfactant. The serum level of GM-CSF autoantibody is the only disease-specific biomarker of autoimmune PAP, although it does not correlate with disease severity. In PAP patients with normal serum GM-CSF autoantibody levels, elevated serum GM-CSF levels is highly suspicious for hereditary PAP. Several biomarkers have been correlated with disease severity, although they are not specific for PAP. These include lactate dehydrogenase, cytokeratin 19 fragment 21.1, carcinoembryonic antigen, neuron-specific enolase, surfactant proteins, Krebs von Lungen 6, chitinase-3-like protein 1 and monocyte chemotactic proteins. Finally, increased awareness of the disease mechanisms has led to the development of pathogenesis-based treatments, such as GM-CSF augmentation and cholesterol-targeting therapies.
