Leveraging blood-based transcriptomics to detect acute cellular rejection in lung transplant

Area of Science:

• Transplantation immunology
• Molecular diagnostics
• Genomics

Background:

• Acute cellular rejection (ACR) significantly impacts long-term survival in lung transplant recipients.
• Chronic allograft dysfunction is a major complication linked to ACR.
• Non-invasive methods for ACR detection are crucial for improved patient outcomes.

Purpose of the Study:

• To develop and validate a blood-based transcriptomic risk score (TRS) for detecting ACR in lung transplant recipients.
• To assess the association between the TRS and ACR.
• To evaluate the diagnostic performance of the TRS for ACR.

Main Methods:

• Analysis of 101 samples from 75 lung transplant recipients.
• Identification of key genes using the least absolute shrinkage and selection operator (LASSO).
• Statistical modeling (logistic mixed model) to associate TRS with ACR, calculating odds ratios (OR) and confidence intervals (CI).

Main Results:

• A novel 4-gene transcriptomic risk score (TRS) was identified.
• The TRS was significantly associated with ACR (OR 3.43, 95% CI 1.86-7.14, p < 0.001).
• The TRS demonstrated strong discriminatory power, with an area under the receiver operator curve (AUC) > 0.8.

Conclusions:

• The blood-based TRS shows potential as a non-invasive tool for diagnosing ACR in lung transplant recipients.
• The TRS may aid in predicting individuals at risk for future ACR.
• Larger studies are warranted to confirm the clinical utility of the TRS for ACR management.