Clinical Examples of the Additive Value of Absolute Quantification of Cell-Free DNA after Heart Transplantation.

Jens Bohmer,Hakan Wahlander,Kristjan Karason,Jan Sunnegardh,Carina Wasslavik,Marianne Jonsson,Julia Asp,Anne Ricksten,Goeran Dellgren

CLINICAL TRANSPLANTATION（2024）

Sahlgrens Univ Hosp

Cited 0|Views6

Abstract

OBJECTIVE:Cell-free DNA (cfDNA) is used as a biomarker after transplantation to detect graft injury, relying on the donor fraction (DF). We have established a PCR-based approach allowing us to separately quantify absolute values of dd-cfDNA and recipient-derived cfDNA (rd-cfDNA). We aimed to present typical clinical scenarios after heart transplantation (HTx) to illustrate the advantages of absolute cfDNA values over DF. METHODS:We used the cfDNA results of our cohort (509 samples of 52 patients followed during the first year after HTx) as background and determined the trajectories of cfDNA in specific clinical situations. We profiled an uncomplicated clinical course, viral and bacterial infections, acute and chronic rejection, and false-negative and false-positive rejections in six patients (five adults, one child). RESULTS:There was a substantial discrepancy between relative (DF) and absolute cfDNA-levels in several clinical situations. Rd- and dd-cfDNA were independently elevated during episodes of rejection and infection and were better suited to depict treatment response than DF alone. CONCLUSIONS:Absolute quantification of cfDNA may offer clinically relevant information additive to DF in various situations after HTx and could be helpful for more accurate monitoring of diagnosis and treatment of rejection.

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Key words

donor-derived cell-free DNA,donor fraction,droplet digital PCR,heart transplantation,rejection,single nucleotide polymorphism

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【要点】：本文提出了一种基于PCR的绝对量化细胞游离DNA（cfDNA）的方法，并通过临床实例展示了其在心脏移植后监测中的优势。

【方法】：研究采用PCR技术分别量化了心脏移植后患者体内的供体来源cfDNA（dd-cfDNA）和受体来源cfDNA（rd-cfDNA）的绝对值。

【实验】：分析了52名患者在心脏移植后第一年的509个cfDNA样本，描述了在无并发症、病毒和细菌感染、急性与慢性排斥反应等特定临床情境下cfDNA的轨迹，并在六名患者中展示了绝对cfDNA值与相对值（DF）之间的显著差异，以及其在诊断和治疗排斥反应中的临床应用。