Donor-Derived Cell-Free DNA Does Not Correlate with Levels of Inflammation or Angiogenesis in a Stable Post Transplant Population

Abstract

Donor-derived cell-free DNA (dd-cfDNA) has recently been introduced as a novel marker of acute cellular and antibody mediated rejection. We hypothesized that levels of dd-cfDNA would correlate with markers of chronic inflammation and angiogenesis in a stable post-transplant population. 65 heart transplant recipients who were 8.5±5.4 years post transplant were enrolled at routine clinic visits. Exclusion criteria for the study were episodes of rejection within 6 months or recent infection. Peripheral blood protein expression of interluekin-6 (IL-6), interluekin-18 (IL-18), tumor necrosis factor-alpha (TNF-α), soluble Fas-ligand (sFASL), angiopoetin-2, vascular endothelial growth factor (VEGF) A, C and D and transforming growth factor alpha (TGF-α) was assessed using a multiplex immunoassay system (Bioplex®). Dd-cfDNA was measured using a targeted amplification, next generation-sequencing assay (AlloSure®; CareDx, Inc.). Patients were stratified for levels of dd-cfDNA % as low and high defined as above (≥0.14%) or below the mean (<0.14%). There were no significant differences in age (p 0.3), left ventricular ejection fraction (p 0.8), episodes of cellular or antibody mediated rejection (p 0.9) or time post transplant (0.3) between the groups. Levels of inflammatory and angiogenesis factors were also similar between the two groups (table 1). Inflammatory and angiogenesis cytokines are not associated with levels of dd-cfDNA in a stable post transplant population. Further studies of should investigate if temporal changes can predict adverse outcomes.