RESUMO
Aims: Early post-transplant complications such as acute graft rejection and infections are associated with high morbidity and mortality of heart and lung transplant recipients who are in vital need of immunosuppressive therapy. MiR-424 is a member of the miR-16 family, which plays an important physiological role in the development of cardiovascular and respiratory pathology, is involved in the regulation of monocyte and macrophage differentiation, and has an immunosuppressive potential. The aim of the study was to determine the diagnostic value of circulating miR-424 as a potential biomarker of post-transplant complications in heart and lung transplant recipients. Methods: The study enrolled 83 heart transplant recipients, aged 18 to 70 (48 ± 13) years; 26 lung transplant recipients, aged 10 to 74 (36 ± 16) years. The miR-424 plasma expression was detected by real-time PCR (Qiagen, USA). Significance of miR-424 level was assessed through the ΔCt method. Acute graft rejection was verified by the results of endomyocardial or transbronchial biopsy. Post-transplant infectious complications were verified through microbiological identification of bacteremia from blood cultures. Results: Our study shows miR-424 upregulation in plasma of patients with chronic heart or respiratory failure in comparison with healthy individuals (p = 0.003 and p = 0.04 resp.). There was a direct correlation of miR-424 expression with red blood cells and hemoglobin levels in patients before heart transplantation (p = 0.01 and p = 0.03 resp.). After transplantation the expression of plasma miR-424 correlated with the level of C-reactive protein (CRP) both in heart (r = 0.75; p = 0.02) and lung (r = 0.50; p = 0.04) transplant recipients. The expression of plasma miR-424 correlated with tacrolimus blood concentration after heart transplantation (r = 0.38; p = 0.04). The miR-424 level didn't differ in heart or lung transplant recipients with and without acute graft rejection (p = 0.47 and p = 0.78 resp.), but was significantly higher in heart and lung transplant recipients with gram-negative bacteremia (p = 0.002). When the miR-424 level is above a threshold value (-5.72 fold change), the relative risk of bacteremia is RR = 3.84 [95% CI 1.94-7.61]; Se = 60.0%; Sp = 89.2%. CRP concentration above 7 mg/L in duplex test with miR-424 improves the diagnostic characteristics of miR-424 for post-transplant gram-negative bacteremia in heart and lung transplant recipients up to RR = 9.17 [95% CI 1.37-61.46]; Se = 83.3% and Sp = 90.1%. Conclusion: MiR-424 plasma expression was upregulated in patients with chronic heart and respiratory failure and in heart and lung transplant recipients in the early post-transplant period. The duplex test, including miR-424 and CRP, has a diagnostic value for detecting the high risk of post-transplant gram-negative bacteremia in heart and lung transplant recipients.
RESUMO
Respiratory complications can be the cause of graft dysfunction after lung transplantation (LTx). MicroRNAs are small regulatory molecules-potential biomarkers of respiratory diseases and post-transplant complications. Galectin-3 is highly expressed in fibrosis of transplanted solid organs. The aim was to evaluate the expression of plasma miR-339 and galectin-3 concentrations in lung recipients including with airway obstruction after LTx. The study included 57 lung recipients (34 men and 23 women aged 10 to 74 years) were followed up to 5 years after LTx. The plasma microRNAs were detected by real-time PCR; galectin-3 levels were measured by ELISA. During follow-up in 30 recipients, post-transplant complications were detected: 12 (40.0%) cases of airway obstruction. The levels of miR-339 and galectin-3 were significantly higher in recipients with airway obstruction compare with 27 (47.3%) recipients without any complications (P = 0.036 and P = 0.014, resp.). Increasing miR-339 (above the 0.02 fold change) and galectin-3 (above the 11.7 ng/ml) threshold plasma levels in lung recipients is associated with high risk (RR = 7.14 ± 0.97 [95% CI 1.05-48.60], P = 0.045) of airway obstruction after LTx. A measurement of miR-339 expression in combination with galectin-3 level might be perspective to identify recipients at risk of airway obstruction after LTx.