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Upregulated circulating mir-424 and its' diagnostic value for gram-negative bacteremia after thoracic transplantation
Olga Shevchenko1,2, Olga Tsirulnikova2,3, Sofya Sharapchenko1
1Department of Regulatory Mechanisms in Transplantology, Shumakov National Medical Research Center of Transplantology and Artificial Organs, Moscow, Russian Federation.
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.
Insights
Circulating miR-424 is upregulated in heart and lung transplant recipients, showing diagnostic value for gram-negative bacteremia. A combined test with C-reactive protein (CRP) improves detection of this high-risk post-transplant complication.
Area of Science:
- Transplantation immunology
- Molecular diagnostics
- Biomarker discovery
Background:
- Early post-transplant complications, including acute graft rejection and infections, significantly increase morbidity and mortality in heart and lung transplant recipients.
- MicroRNA-424 (miR-424), a member of the miR-16 family, plays a role in cardiovascular and respiratory pathology and possesses immunosuppressive potential.
- Identifying reliable biomarkers for early detection of post-transplant complications is crucial for improving patient outcomes.
Purpose of the Study:
- To evaluate the diagnostic utility of circulating miR-424 as a potential biomarker for post-transplant complications in heart and lung transplant recipients.
- To investigate the correlation of miR-424 levels with clinical parameters and outcomes in transplant patients.
Main Methods:
- Plasma miR-424 expression was quantified using real-time PCR in 83 heart and 26 lung transplant recipients.
- miR-424 levels were assessed using the ΔCt method and correlated with clinical data, including graft rejection (biopsy), infections (blood cultures), C-reactive protein (CRP), and tacrolimus concentration.
- Diagnostic performance of miR-424, alone and in combination with CRP, for gram-negative bacteremia was analyzed.
Main Results:
- miR-424 was significantly upregulated in plasma of patients with chronic heart/respiratory failure and in transplant recipients post-transplant compared to healthy individuals.
- Plasma miR-424 levels correlated with C-reactive protein (CRP) in both heart and lung transplant recipients and with tacrolimus blood concentration in heart recipients.
- miR-424 was significantly higher in patients with gram-negative bacteremia. A duplex test with miR-424 and CRP demonstrated high diagnostic accuracy for post-transplant gram-negative bacteremia.
Conclusions:
- Circulating miR-424 is upregulated in patients with chronic heart/respiratory failure and in the early post-transplant period.
- Plasma miR-424 shows diagnostic value for detecting high-risk post-transplant gram-negative bacteremia.
- A combined diagnostic test utilizing miR-424 and CRP offers improved accuracy for identifying gram-negative bacteremia in heart and lung transplant recipients.
