Abstract: SA-PO0989
Donor-Derived Cell-Free DNA for Post-Transplant Assessment in a Patient with Trisomy 21
Session Information
- Transplantation: Clinical - Case Reports
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Transplantation
- 2102 Transplantation: Clinical
Authors
- Pozo Garcia, Leonardo, Arizona Kidney Disease and Hypertension Center, Tucson, Arizona, United States
- Severe, Bailey, Natera, Inc., Austin, Texas, United States
- Ahmed, Ebad, Natera, Inc., Austin, Texas, United States
- Xie, Jing, Natera, Inc., Austin, Texas, United States
Introduction
Donor-derived cell-free DNA (dd-cfDNA) is a validated biomarker for detecting allograft rejection in kidney, heart, and lung transplant recipients. Single nucleotide polymorphism (SNP)-based sequencing technology enables differentiation between recipient- and donor-derived cfDNA, allowing accurate quantification of the dd-cfDNA fraction. However, SNP-based dd-cfDNA measurements may be influenced by factors such as pregnancy, multiple organ transplants, and or large chromosomal abnormalities in the recipient. When such conditions are indicated by the genetic data, the testing laboratory contacts the ordering physician to ensure proper interpretation of the test results. Here we discuss a case in which a copy number change detected in recipient cfDNA was ultimately identified to be Trisomy 21.
Case Description
A 35 year-old male with a history of end-stage renal disease due to posterior urethral valves underwent two kidney transplants - the first in 1996, and a second in 2011. dd-cfDNA testing was performed in February and April of 2025, with results indicating a low risk of rejection (0.78% and 0.80% dd-cfDNA%, respectively). During manual data review, skewed SNP variant allele frequencies were observed across chromosome 21, suggestive of a large copy number alteration. This raised concerns for potential underlying conditions, including malignancy and aneuploidy. The testing laboratory notified the clinic, who confirmed that the patient had no known malignancy, but did have a diagnosis of Trisomy 21, which was consistent with the observed genetic pattern. A fine-tuned algorithm designed for cases with aneuploidy confirmed that the impact on dd-cfDNA quantification by T21 was minimal, with less than a 10% relative difference, and did not affect the clinical interpretation of the test.
Discussion
cfDNA testing has been widely adopted in the transplant, prenatal, and oncology fields due to its ability to determine clinical useful characteristics based on donor organ, fetus, and cancer cfDNA. It is critical that cfDNA testing methodologies are robust against additional and unexpected sources of cfDNA. This case highlights the importance of considering constitutional genetic conditions, such as aneuploidy, during the analysis of cfDNA results to ensure accurate clinical assessment.