ORIGINAL RESEARCH article
Front. Med.
Sec. Pulmonary Medicine
Volume 12 - 2025 | doi: 10.3389/fmed.2025.1650830
This article is part of the Research TopicAdvancing the Early Diagnosis of Interstitial Lung Diseases – Beyond ILAsView all articles
Hyaluronan in the pathogenesis of lung fibrosis associated to autoimmune Pulmonary Alveolar Proteinosis (aPAP)
Provisionally accepted
Raffaele Gentile1
Vincenzo Alfredo Marando2Francesca Mariani2
Sara Lettieri2Matteo Della Zoppa2
Michele Zorzetto1Laura Maria Ciardelli1Riccardo Albertini1
Annalisa De Silvestri3
ANGELO GUIDO CORSICO2,4
Ilaria Campo2*- 1Laboratory of Clinical Chemistry, IRCCS Policlinico San Matteo Foundation, Pavia, Italy
- 2Pneumology Unit, IRCCS Policlinico San Matteo Foundation, Pavia, Italy
- 3Clinical Epidemiology and Biometric Unit, IRCCS Policlinico San Matteo Foundation, Pavia, Italy
- 4University of Pavia, Pavia, Italy
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
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.Aim:To investigate serum biomarkers as prognostic factor of lung fibrosis in aPAP.Methods: 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 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 Eliminato: keyword5 35
Keywords: PAP, lung fibrosis, ELF, hyaluronan, Serum biomarkers. (Min.5-Max. 8
Received: 20 Jun 2025; Accepted: 11 Aug 2025.
Copyright: © 2025 Gentile, Marando, Mariani, Lettieri, Della Zoppa, Zorzetto, Ciardelli, Albertini, De Silvestri, CORSICO and Campo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Ilaria Campo, Pneumology Unit, IRCCS Policlinico San Matteo Foundation, Pavia, Italy
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.