Immunologic responses to antifibrotic treatment in IPF patients

• Published in: International immunopharmacology Vol. 95; p. 107525
• Main Authors: d'Alessandro, Miriana, Bergantini, Laura, Cameli, Paolo, Fanetti, Matteo, Alderighi, Lorenzo, Armati, Martina, Refini, Rosa Metella, Alonzi, Valerio, Sestini, Piersante, Bargagli, Elena
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.06.2021; Elsevier BV
• Subjects: Biomarkers; CD1d antigen; CD25 antigen; CD4 antigen; CD45RA antigen; CD5 antigen; Effector cells; Fibrosis; Follicular cells; Helper cells; Immunology; IPF; Lung diseases; Lymphocytes T; Nintedanib; Peripheral blood; Phenotypes; Regulatory cells; Response to treatment; Therapy; ILD; CD; Regulatory cells; Treg; Nintedanib; AUROC; Follicular cells; Breg; CCR; Th; Tfh; Biomarkers; Response to treatment; CXCR; IPF
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2021.107525

•The immunological dysregulation linked to IPF onset and progression is still not clear.•Immunological biomarkers were identified in peripheral blood after 1 year of antifibrotic therapy.•Predictive biomarkers of response to antifibrotic treatment were evaluated.•Nintedanib significantly helps to restore immunological responses in IPF patients. Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease limited to the lungs. Immunological dysregulation may significantly participate in the pathophysiology of IPF. The immunological responses to nintedanib therapy in IPF patients were investigated for the first time in this study. Fifty IPF patients (median age (IQR) 69 (65–75) years; 38 males), were selected retrospectively. Flowcytometry analysis were performed to phenotype immunological biomarkers in peripheral blood from IPF patients after 1 year of antifibrotic therapy and a group of healthy volunteers. Before starting antifibrotic treatment, IPF patients showed increased CD1d+CD5+ (p = 0.0460), Treg (p = 0.0354), T effector (CD25highCD127high) (p = 0.0336), central cells (CD4+CD45RA−) (p = 0.0354), effector cells (CD4+CD45RA+) (p = 0.0249) and follicular cell percentages (p = 0.0006), notably Tfh1 (p = 0.0412) and Tfh17 (p = 0.0051) cell percentages, in respect with healthy controls (HC). After nintedanib therapy, Breg (p = 0.0302), T effector (p = 0.0468), Th17.1 (p = 0.0146) and follicular cells (p = 0.0006), notably Tfh1 (p = 0.0006) and Tfh17 (p = 0.0182) cell percentages, were significantly decreased. In the logistic regression, Tfh panel showed a significant area under the receiver operating characteristics curve (AUROC) to distinguish IPF than HC (90.5%), as well as t0 and t1 (99.3%). In conclusion, the immunological results obtained in this study demonstrate that nintedanib significantly helps to restore immunological responses in IPF patients. These findings will be useful in the search for biomarkers predictive of response to antifibrotic treatment.