Donor-derived cell-free DNA in chronic lung allograft dysfunction phenotypes: a pilot study.

Area of Science:

• Transplantation Immunology
• Biomarker Discovery
• Genomics

Background:

• Chronic lung allograft dysfunction (CLAD) limits long-term survival post-lung transplantation.
• CLAD presents as bronchiolitis obliterans syndrome (BOS) or restrictive allograft syndrome (RAS).
• Donor-derived cell-free DNA (dd-cfDNA) may indicate subclinical allograft injury.

Purpose of the Study:

• To assess plasma dd-cfDNA levels as a biomarker for lung allograft health.
• To evaluate dd-cfDNA across stable, preclinical, and established CLAD stages.
• To compare dd-cfDNA in BOS and RAS phenotypes.

Main Methods:

• Prospective study of 20 lung transplant recipients with CLAD.
• Collected plasma samples at three time points: stable, preclinical CLAD, and established CLAD.
• Measured dd-cfDNA levels, excluding concurrent infection or acute rejection.

Main Results:

• Elevated dd-cfDNA detected in 47% of stable, 66% of preclinical, and 71% of established CLAD samples.
• dd-cfDNA levels indicated ongoing allograft injury across CLAD spectrum.
• High intra- and interpatient variability observed; no significant difference between BOS and RAS (p=0.25), though higher range in RAS.

Conclusions:

• dd-cfDNA can detect ongoing allograft injury in CLAD patients.
• Further research is needed to improve early CLAD detection using dd-cfDNA.
• Variability in dd-cfDNA requires further investigation for clinical utility.