부산대학교 도서관

There is a clear need for a non-invasive biomarker that could allow surveillance of acute cellular rejection (ACR) without the need of repeated endomyocardial biopsies (EMB) in heart transplant (HT) recipients. Donor-derived cell-free DNA (dd-cfDNA) is currently under study for this purpose. This was a multicenter, observational, prospective study. According to protocol, all patients included underwent surveillance EMB at 15 days, 1, 2, 3, 4, 6 and 12 months post-HT. Dd-cfDNA levels were determined prior to each EMB, using Next Generation Sequencing technology (Allonext® assay, Eurofins Genome). Primary end-point was the association between dd-cfDNA levels and the presence of ACR, as determined by ISHLT 2004 classification. We herein report the results of the first 848 pairs of EMB-dd-cfDNA determinations. The cohort included 206 recipients from 12 different centers (mean age 54 ± 11 years, 73% male). ACR, defined as grade ≥2R, was present in 35 EMB (4.1%), and AMR ≥1 in 14 EMB (1.7%). Median dd-cfDNA values for each ACR group were: 0R 0.088% (0.038-0.22), 1R 0.15% (0.056-0.4), 2R 0.23% (0.06-0.6) and 3R 0.6%. AMR0 median (IQR) values were 0.1% (0.04-0.24), and AMR≥1, 0.2% (0.075-0.7), respectively. In order to reduce the skewness, %ddcfDNA was logtransformed as log2(x+0.01) (Figure 1A). Using a GEE (generalized estimating equation) model, we found a statistically significant association between %dd-cfDNA and ACR ≥2R (OR 1.23, IQR 1.04-1.45), p <0.01 (Figure 1B). A 0.15% ddcf-DNA threshold revealed a negative predictive value of 97%, and could allow to save 57% of surveillance EMB. Dd-cfDNA appears to be an excellent biomarker for acute cellular rejection. Its high negative predictive value could allow to eliminate the need to perform a significant percentage of surveillance EMB currently performed in HT recipients. [ABSTRACT FROM AUTHOR]