Abstract
Donor-derived cell-free DNA (dd-cf-DNA) has been shown to be an informative biomarker of rejection after lung transplantation (LT) from deceased donors. However, in living-donor lobar LT, because small grafts from blood relatives are implanted with short ischemic times, the detection of dd-cf-DNA might be challenging. Our study was aimed at examining the role of dd-cf-DNA measurement in the diagnosis of primary graft dysfunction and acute rejection early after living-donor lobar LT. Immediately after LT, marked increase of the plasma dd-cf-DNA levels was noted, with the levels subsequently reaching a plateau with the resolution of primary graft dysfunction. Increased plasma levels of dd-cf-DNA were significantly correlated with decreased oxygenation immediately (p = 0.022) and at 72 hours (p = 0.046) after LT. Significantly higher plasma dd-cf-DNA levels were observed in patients with acute rejection (median, 12.0%) than in those with infection (median, 4.2%) (p = 0.028) or in a stable condition (median, 1.1%) (p = 0.001). Thus, measurement of the plasma levels of dd-cf-DNA might be useful to monitor the severity of primary graft dysfunction, and plasma dd-cf-DNA could be a potential biomarker for the diagnosis of acute rejection after LT.
Highlights
Long-term survival after lung transplantation (LT) has been worse than that after other solid organ transplantations[1,2,3]
In the infection and rejection groups, none of the patients developed any complications until postoperative day (POD) 6 after living-donor lobar LT (LDLLT), but subsequently, infection or acute rejection (AR) developed between POD7 and POD14
The plasma dd-Cell-free DNA (cf-DNA) levels were significantly negatively correlated with the P/F ratio on POD 0 and POD 3 after LDLLT, suggesting that elevated dd-cf-DNA levels could be associated with decreased oxygenation of the transplanted lungs caused by primary graft dysfunction after LDLLT
Summary
Long-term survival after lung transplantation (LT) has been worse than that after other solid organ transplantations (median survival: lung 6.0 years, heart 10.7 years, liver 8.5 years)[1,2,3]. Measurement of the plasma level of donor-derived cell-free DNA (dd-cf-DNA) was shown to be useful as a noninvasive diagnostic test for AR after cadaveric LT10. Cell-free DNA (cf-DNA) consists mainly of 166 base-pair double-stranded DNA fragments resulting from apoptosis, necrosis or release of nuclear DNA into the circulation[8,9]. In the circulation, these fragments have a short half-life of 1.5 hours, because of rapid hepatic and renal clearance[11].
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