The Role of Galectins in Chronic Lung Allograft Dysfunction

Abstract

Background Galectins are proteins that bind β-galactosides such as N-acetyllactosamine present in N-linked and O-linked glycoproteins and that seem to be implicated in inflammatory and immune responses as well as fibrotic mechanisms. This preliminary study investigated serum galectins as clinical biomarkers in lung transplant patients with chronic lung allograft dysfunction (CLAD), phenotype bronchiolitis obliterans syndrome (BOS). Materials and Methods Nineteen lung transplant patients [median age (IQR), 55 (45–62) years; 53% males] were enrolled in the study. Peripheral blood concentrations of galectins-1, 3 and 9 were determined with commercial ELISA kits. Results Galectin-1 concentrations were higher in BOS than in stable LTX patients (p = 0.0394). In logistic regression analysis, testing BOS group as dependent variable with Gal-1 and 3 as independent variables, area under the receiver operating characteristics (AUROC) curve was 98.9% (NPV 90% and PPV 88.9%, p = 0.0003). With the stable LTX group as dependent variable and Gal-1, 3 and 9 as independent variables, AUROC was 92.6% (NPV 100% and PPV 90%, p = 0.0023). In stable patients were observed an inverse correlation of Gal-3 with DLCO% and KCO%, and between Gal-9 and KCO%. Conclusion Galectins-1, 3 and 9 are possible clinical biomarkers in lung transplant patients with diagnostic and prognostic meaning. These molecules may be directly implicated in the pathological mechanisms of BOS. The hypothesis that they could be new therapeutic targets in BOS patients is intriguing and also worth exploring.

Proteomic analysis of transbronchial biopsy tissue reveals a distinct proteome and mechanistic pathways in high-grade eosinophilic inflammation after lung transplantation

“…To support it, a growing number of studies reported a signi cant relationship between elevated Gal-3 concentrations and higher risk of graft rejection and death in transplant recipients (27,28). For example, d'Alessandro et al, (29) observed higher serum concentrations of Gal-3 in CLAD patients than in healthy controls that indicates the relationship between Gal-3 and CLAD development. Higher plasma level of Gal-3 was also reported to induce myocardial brosis, acute graft rejection and the number of rejection episodes after heart transplantation (30).…”

MiR‐339 and galectin‐3: diagnostic value in patients with airway obstruction after lung transplantation

“…This result coincided as data in study by d’Alessandro et al . but we did not assess the pathological mechanism of complications; diagnosis was verified by transbronchial biopsy [27]. However, the number of individuals enrolled in this study is relatively small; therefore, our findings need to be replicated in a larger cohort of patients.…”

Common Molecular Pathways Between Post-COVID19 Syndrome and Lung Fibrosis: A Scoping Review

“…Indeed, the study by Garcia-Revilla J, Deierborg T et al (Garcia-Revilla et al, 2020) points out how Gal3 appears to be elevated in proliferative T lymphocytes associated with severe COVID-19 and that in a subset of pro-fibrogenic macrophages, Gal3 was one of the most upregulated genes in association with TREM2 and SPP1, both of which are involved in the disease and in pulmonary fibrosis. Furthermore, it has also been reported that SARS-CoV-2, like the H5N1 influenza virus, can activate the NLRP3 inflammasome by exploiting the action of Gal3 which in turn governs the release of proinflammatory cytokines such as: IL-1, IL-6, TNFα and IL-1β (d'Alessandro et al, 2020b;Garcia-Revilla et al, 2020;d'Alessandro et al, 2021c).…”