Noninvasive Transplant Rejection Detection Using cfDNA and TTV Biomarkers
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Solution Overview
Problem
Current methods for detecting graft injury and rejection in transplant recipients are invasive, costly, and often lead to late diagnosis, necessitating a more sensitive and specific non-invasive test.
Innovation Solution
The method involves measuring Torque teno virus (TTV) and donor-derived cell-free DNA in blood, plasma, or urine samples, using high-throughput sequencing to quantify these markers and determine their ratios, which serve as biomarkers for rejection and immunosuppression, allowing for early detection of transplant rejection.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If biopsy-based tests are used for detecting transplant rejection, then diagnostic accuracy is achieved, but the method is invasive and costly
Solution Approach 1:
The patent uses cell-free DNA (cfDNA) as an intermediary biomarker that reflects graft injury without requiring direct tissue sampling. The cfDNA serves as a mediator between the transplant organ status and the diagnostic test, allowing non-invasive detection of rejection through blood or urine samples while maintaining diagnostic accuracy
Solution Approach 2:
The patent replaces the mechanical biopsy procedure with a biochemical assay. Instead of physically sampling tissue through invasive procedures, the method uses molecular detection of cfDNA fragments in body fluids to diagnose rejection, substituting mechanical tissue extraction with chemical/biological marker analysis
2Reliability
If biopsy-based tests are used for detecting transplant rejection, then diagnostic capability is maintained, but the diagnosis is delayed
Solution Approach 1:
The patent enables early detection by monitoring cfDNA levels continuously in body fluids, allowing preliminary identification of rejection trends before clinical symptoms manifest. The method detects subtle changes in cfDNA fragmentation patterns that precede overt rejection, enabling earlier intervention
Solution Approach 2:
The patent establishes continuous monitoring of cfDNA biomarkers through repeated non-invasive sampling, maintaining ongoing assessment of graft health. This continuous detection capability allows real-time tracking of rejection progression or resolution, unlike periodic biopsy schedules that may miss transient rejection events
3Reliability
If invasive biopsy-based tests are used, then rejection detection is achieved, but costs increase
Solution Approach 1:
The patent employs disposable cfDNA extraction and analysis protocols that are less resource-intensive than biopsy procedures. The method uses standard blood or urine collection tubes and automated cfDNA quantification assays, eliminating the need for specialized biopsy equipment, pathologist time, and complex tissue processing infrastructure
Data Source
AI summary
The present disclosure provides methods for preparation and analysis of biological samples of transplant recipients for determination of transplant rejection, comprising: (a) measuring the amount of Torque teno virus (TTV) in a blood, plasma, serum, or urine sample of a transplant recipient; (b) measuring the amount of donor-derived cell-free DNA in a blood, plasma, serum, or urine sample of the transplant recipient; and (c) determining whether the amount of donor-derived cell-free DNA or a function thereof exceeds a cutoff threshold indicating transplant rejection and whether the transplant recipient has an increased or decreased amount of TTV indicating decreased or increased immune response, respectively.