Decreased Serum Levels of Irisin are Associated with the Development of Chronic Lung Allograft Dysfunction after Bilateral Living-Donor Lobar Lung Transplantation

Abstract

Purpose Irisin is a skeletal muscle cell-derived myokine associated with physical activity. Recently, decreased serum irisin levels have been shown to cause alveolar epithelial apoptosis resulting in lung emphysema in patients with chronic obstructive pulmonary disease. Similar to the patients with emphysema, the patients with chronic lung allograft dysfunction (CLAD) after living-donor lobar lung transplantation (LDLLT) could show emphysematous changes, because in LDLLT, small lobar grafts expand to fit into the recipient's chest cavity due to the size mismatch. However, the relationship between serum irisin levels and CLAD after LDLLT remains unknown. Methods Blood samples were collected from a total of 33 patients who underwent bilateral LDLLT, including patients with CLAD (the CLAD group, n=11) and those without CLAD (the non-CLAD group, n=22). Serum samples were assayed for irisin using ELISA kit and compared between the two groups. Appropriate cut-off values of irisin level were set for the diagnosis of CLAD. Results The median follow-up period was 4366 (1055-7180) days. Serum irisin levels of the CLAD group were significantly lower than those of the non-CLAD group (9.5 ± 3.4 vs. 13.2 ± 4.2 ng/mL, P = 0.018) (Fig. 1). An ROC analysis of the performance of the serum irisin level as a marker of CLAD yielded an AUC of 0.76 (sensitivity=0.91 and specificity=0.64 at a threshold level of 12.6 ng/mL). Moreover, patients with irisin level ≥12.6 ng/mL (n=16) showed significantly better CLAD-free survival than those with irisin level Conclusion Decreased serum irisin levels are associated with the development of CLAD after bilateral LDLLT. Irisin might be a novel biomarker for the diagnosis of CLAD after LDLLT.