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Potential novel biomarkers for chronic lung allograft dysfunction and azithromycin responsive allograft dysfunction
Cecilia Veraar1, Jonathan Kliman2, Alberto Benazzo2
1Division of Cardiac Thoracic Vascular Anaesthesia and Intensive Care Medicine, Department of Anaesthesiology, General Intensive Care and Pain Medicine, Medical University of Vienna, Vienna, Austria.
Scientific Reports
|March 25, 2021
Summary
New biomarkers, Lipocalin-2 and Activin-A, can predict Chronic Lung Allograft Dysfunction (CLAD) after lung transplantation. These markers help differentiate CLAD subtypes and may improve patient outcomes.
Area of Science:
- Immunology
- Transplantation Medicine
- Pulmonary Medicine
Background:
- Chronic Lung Allograft Dysfunction (CLAD) is a primary cause of poor long-term outcomes post-lung transplantation (LTX).
- Current diagnostic methods lack specific biomarkers to differentiate between CLAD phenotypes like Bronchiolitis Obliterans Syndrome (BOS) and Restrictive Allograft Syndrome (RAS).
- Identifying distinct biomarkers could aid in early detection and tailored treatment strategies for CLAD.
Purpose of the Study:
- To identify specific serum cytokines that can differentiate between BOS, RAS, and Azithromycin-Responsive Allograft Dysfunction (ARAD).
- To investigate potential similarities between CLAD phenotypes and end-stage fibrotic diseases.
- To evaluate the predictive value of identified biomarkers for CLAD development in stable lung transplant recipients.
Main Methods:
- Serum samples from lung transplant recipients with different CLAD phenotypes (BOS, RAS, ARAD) and stable controls were analyzed.
- Cytokine concentrations, including Lipocalin-2 and Activin-A, were measured using immunoassays.
- Immunohistochemistry was employed to localize biomarker expression in lung tissue from RAS patients.
- Statistical analysis was performed to assess biomarker significance and predictive value.
Main Results:
- Significantly elevated serum Lipocalin-2 concentrations were observed in RAS patients compared to BOS patients.
- Lipocalin-2 expression was detected in the bronchial epithelium and alveolar walls of RAS patients.
- ARAD patients exhibited significantly lower serum Activin-A concentrations than stable LTX and BOS patients.
- Increased serum Lipocalin-2 and Activin-A levels were associated with a higher risk of developing CLAD in stable LTX patients.
Conclusions:
- Lipocalin-2 and Activin-A show promise as serum biomarkers for predicting and differentiating CLAD phenotypes.
- These biomarkers may facilitate earlier diagnosis and personalized management of lung transplant recipients.
- Further clinical validation is warranted for the implementation of these biomarkers in routine practice.

