Date: Monday, June 3, 2019
Session Time: 2:30pm-4:00pm
Presentation Time: 2:54pm-3:06pm
Location: Veterans Auditorium
*Purpose: We hypothesize that subclinical inflammation, resulting in molecular injury, may contribute to sensitization of the recipients’ immune system. Antigenic presentation of donor-derived nucleic acids, as reflected by elevated donor derived cell free DNA (dd-cfDNA) levels, may lead to leucocyte activation, promoting cytokine release and donor specific antibody (DSA) formation.
*Methods: Retrospective cohort analysis using the Circulating Donor-Derived Cell-Free DNA in Blood for Diagnosing Acute Rejection in Kidney Transplant Recipients (DART Study) data set. 789 samples from 185 kidney transplant patients with dd-cfDNA (AlloSure) results and DSA status known, within the first 24 months following transplant were identified. dd-cfDNA was correlated with DSA mean fluorescence intensity (MFI). Mann Whitney U, Kruskal-Wallis, Spearman rank and linear regression were used, with results plotted on logarithmic scales.
*Results: 474 samples (60.1%) had negative DSA, with a median dd-cfDNA = 0.20% (IQR 0.10% – 0.34%), 257 samples (32.6%) had pre-formed DSA with a median dd-cfDNA = 0.30% (IQR 0.12% – 0.75%). 58 patients (7.4 %) had de-novo DSA formation, median dd-cfDNA = 0.57%, (IQR 0.24% – 1.48%) DSA negative patients had significantly lower dd-cfDNA levels than patients who were DSA positive (p< 0.001) while patients with de-novo DSA had significantly higher dd-cfDNA than patients who had pre-formed DSA. (p= 0.001) DSA MFI had a positive correlation with dd-cfDNA levels (r=0.30 CI - 0.083 to 0.466 p=0.004), with 99% of the MFIs being greater than 500. Logistic modeling with multivariate analysis showed dd-cfDNA is independently a predictor of de-novo DSA, when controlling for race, age, donor type and, prior transfusion, and HLA mismatch (1-6) (p < 0.001).
*Conclusions: Higher dd-cfDNA levels are associated with de-novo DSA formation. The exact mechanism remains to be elucidated. Prospective dd-cfDNA monitoring, with immunosuppression augmentation in response to dd-cfDNA levels, may be beneficial in patients deemed at risk in the absence of clinical symptoms or biopsy findings.
To cite this abstract in AMA style:Jordan S, Sawinski D, Dholakia S. Donor Derived Cell Free DNA Initiates De-Novo Donor Specific Antibody (DSA) Responses [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/donor-derived-cell-free-dna-initiates-de-novo-donor-specific-antibody-dsa-responses/. Accessed November 29, 2020.
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