Cell-Free Dna As A Solid-Organ Transplant Biomarker: Technologies and Approaches

References

• Loupy A , AubertO, ReesePP, BastienO, BayerF, JacquelinetC. Organ procurement and transplantation during the COVID-19 pandemic. Lancet395(10237), e95–e96 (2020).
   PubMed Web of Science ®Google Scholar
• Lodhi SA , LambKE, Meier-KriescheHU. Solid organ allograft survival improvement in the United States: the long-term does not mirror the dramatic short-term success. Am. J. Transplant11(6), 1226–1235 (2011).
   PubMed Web of Science ®Google Scholar
• Rana A , GodfreyEL. Outcomes in solid-organ transplantation: success and stagnation. Tex. Heart Inst. J.46(1), 75–76 (2019).
   PubMed Web of Science ®Google Scholar
• Cozzi E , ColpoA, DeSilvestro G. The mechanisms of rejection in solid organ transplantation. Transfus. Apher. Sci.56(4), 498–505 (2017).
   PubMed Web of Science ®Google Scholar
• Gwinner W . Renal transplant rejection markers. World J. Urol.25(5), 445–455 (2007).
   PubMed Web of Science ®Google Scholar
• Josephson MA . Monitoring and managing graft health in the kidney transplant recipient. Clin. J. Am. Soc. Nephrol.6(7), 1774–1780 (2011).
   PubMed Web of Science ®Google Scholar
• Massoud O , HeimbachJ, VikerKet al. Noninvasive diagnosis of acute cellular rejection in liver transplant recipients: a proteomic signature validated by enzyme-linked immunosorbent assay. Liver Transpl.17(6), 723–732 (2011).
   PubMedGoogle Scholar
• Kindel SJ , HsuHH, HussainT, JohnsonJN, McmahonCJ, KuttyS. Multimodality noninvasive imaging in the monitoring of pediatric heart transplantation. J. Am. Soc. Echocardiogr.30(9), 859–870 (2017).
   PubMed Web of Science ®Google Scholar
• Butler CR , SavuA, BakalJAet al. Correlation of cardiovascular magnetic resonance imaging findings and endomyocardial biopsy results in patients undergoing screening for heart transplant rejection. J. Heart Lung Transplant.34(5), 643–650 (2015).
   PubMed Web of Science ®Google Scholar
• Ochman M , WojarskiJ, WiorekAet al. Usefulness of the impulse oscillometry system in graft function monitoring in lung transplant recipients. Transplant Proc.50(7), 2070–2074 (2018).
   PubMed Web of Science ®Google Scholar
• Gielis EM , LedeganckKJ, DeWinter BYet al. Cell-free DNA: an upcoming biomarker in transplantation. Am. J. Transplant15(10), 2541–2551 (2015).
   PubMed Web of Science ®Google Scholar
• Lo YM , TeinMS, PangCC, YeungCK, TongKL, HjelmNM. Presence of donor-specific DNA in plasma of kidney and liver-transplant recipients. Lancet351(9112), 1329–1330 (1998).
   PubMed Web of Science ®Google Scholar
• Mandel P , MetaisP. Nuclear acids in human blood plasma. CR Seances Soc. Biol. Fil.142(3–4), 241–243 (1948).
   PubMedGoogle Scholar
• Szilagyi M , PosO, MartonEet al. Circulating cell-free nucleic acids: main characteristics and clinical application. Int. J. Mol. Sci.21(18), 6827 (2020).
   PubMed Web of Science ®Google Scholar
• Bronkhorst AJ , UngererV, HoldenriederS. Early detection of cancer using circulating tumor DNA: biological, physiological and analytical considerations. Crit. Rev. Clin. Lab. Sci. doi:10.1080/10408363.2019.17009021–17 (2019) ( Epub ahead of print).
   Web of Science ®Google Scholar
• Khier S , LohanL. Kinetics of circulating cell-free DNA for biomedical applications: critical appraisal of the literature. Future Sci. OA4(4), FSO295 (2018).
   PubMed Web of Science ®Google Scholar
• Mouliere F , RobertB, ArnauPeyrotte Eet al. High fragmentation characterizes tumour-derived circulating DNA. PLoS ONE6(9), e23418 (2011).
   PubMed Web of Science ®Google Scholar
• Gall TMH , BeleteS, KhanderiaE, FramptonAE, JiaoLR. Circulating tumor cells and cell-free DNA in pancreatic ductal adenocarcinoma. Am. J. Pathol.189(1), 71–81 (2019).
   PubMed Web of Science ®Google Scholar
• Martuszewski A , PaluszkiewiczP, KrolM, BanasikM, KepinskaM. Donor-derived cell-free DNA in kidney transplantation as a potential rejection biomarker: a systematic literature review. J. Clin. Med.10(2), 193 (2021).
   PubMed Web of Science ®Google Scholar
• Burnham P , KimMS, Agbor-EnohSet al. Single-stranded DNA library preparation uncovers the origin and diversity of ultrashort cell-free DNA in plasma. Sci. Rep.6, 27859 (2016).
   PubMed Web of Science ®Google Scholar
• Fairbrother G , JohnsonS, MusciTJ, SongK. Clinical experience of noninvasive prenatal testing with cell-free DNA for fetal trisomies 21, 18, and 13, in a general screening population. Prenat. Diagn.33(6), 580–583 (2013).
   PubMed Web of Science ®Google Scholar
• Ryan A , HunkapillerN, BanjevicMet al. Validation of an enhanced version of a single-nucleotide polymorphism-based noninvasive prenatal test for detection of fetal aneuploidies. Fetal Diagn. Ther.40(3), 219–223 (2016).
   PubMed Web of Science ®Google Scholar
• Schwarzenbach H , HoonDS, PantelK. Cell-free nucleic acids as biomarkers in cancer patients. Nat. Rev. Cancer11(6), 426–437 (2011).
   PubMed Web of Science ®Google Scholar
• Bloom RD , BrombergJS, PoggioEDet al. Cell-free DNA and active rejection in kidney allografts. J. Am. Soc. Nephrol.28(7), 2221–2232 (2017).
   PubMed Web of Science ®Google Scholar
• Sigdel TK , ArchilaFA, ConstantinTet al. Optimizing detection of kidney transplant injury by assessment of donor-derived cell-free DNA via massively multiplex PCR. J. Clin. Med.8(1), 19 (2018).
   PubMed Web of Science ®Google Scholar
• Stewart CM , KothariPD, MouliereFet al. The value of cell-free DNA for molecular pathology. J. Pathol.244(5), 616–627 (2018).
   PubMed Web of Science ®Google Scholar
• Baxter-Lowe LA , BuschMP. Tracking microchimeric DNA in plasma to diagnose and manage organ transplant rejection. Clin. Chem.52(4), 559–561 (2006).
   PubMed Web of Science ®Google Scholar
• Lee TH , MontalvoL, ChrebtowV, BuschMP. Quantitation of genomic DNA in plasma and serum samples: higher concentrations of genomic DNA found in serum than in plasma. Transfusion41(2), 276–282 (2001).
   PubMed Web of Science ®Google Scholar
• Alidousty C , BrandesD, HeydtCet al. Comparison of blood collection tubes from three different manufacturers for the collection of cell-free DNA for liquid biopsy mutation testing. J. Mol. Diagn.19(5), 801–804 (2017).
   PubMed Web of Science ®Google Scholar
• Meddeb R , PisarevaE, ThierryAR. Guidelines for the preanalytical conditions for analyzing circulating cell-free DNA. Clin. Chem.65(5), 623–633 (2019).
   PubMed Web of Science ®Google Scholar
• Medina Diaz I , NoconA, MehnertDH, FredebohmJ, DiehlF, HoltrupF. Performance of Streck cfDNA blood collection tubes for liquid biopsy testing. PLoS ONE11(11), e0166354 (2016).
   PubMed Web of Science ®Google Scholar
• Zhao Y , LiY, ChenP, LiS, LuoJ, XiaH. Performance comparison of blood collection tubes as liquid biopsy storage system for minimizing cfDNA contamination from genomic DNA. J. Clin. Lab. Anal.33(2), e22670 (2019).
   PubMed Web of Science ®Google Scholar
• North PE , ZieglerE, MahnkeDKet al. Cell-free DNA donor fraction analysis in pediatric and adult heart transplant patients by multiplexed allele-specific quantitative PCR: validation of a rapid and highly sensitive clinical test for stratification of rejection probability. PLoS ONE15(1), e0227385 (2020).
   PubMed Web of Science ®Google Scholar
• Sorber L , ZwaenepoelK, JacobsJet al. Circulating cell-free DNA and RNA analysis as liquid biopsy: optimal centrifugation protocol. Cancers (Basel)11(4), 458 (2019).
   PubMed Web of Science ®Google Scholar
• Sorber L , ZwaenepoelK, DeschoolmeesterVet al. A comparison of cell-free dna isolation kits: isolation and quantification of cell-free DNA in plasma. J. Mol. Diagn.19(1), 162–168 (2017).
   PubMed Web of Science ®Google Scholar
• Markus H , Contente-CuomoT, FarooqMet al. Evaluation of pre-analytical factors affecting plasma DNA analysis. Sci. Rep.8(1), 7375 (2018).
   PubMedGoogle Scholar
• Beck J , OellerichM, SchulzUet al. Donor-derived cell-free DNA is a novel universal biomarker for allograft rejection in solid organ transplantation. Transplant. Proc.47(8), 2400–2403 (2015).
   PubMed Web of Science ®Google Scholar
• Shen J , ZhouY, ChenYet al. Dynamics of early post-operative plasma ddcfDNA levels in kidney transplantation: a single-center pilot study. Transpl. Int.32(2), 184–192 (2019).
   PubMed Web of Science ®Google Scholar
• Gielis EM , BeirnaertC, DendoovenAet al. Plasma donor-derived cell-free DNA kinetics after kidney transplantation using a single tube multiplex PCR assay. PLoS ONE13(12), e0208207 (2018).
   PubMed Web of Science ®Google Scholar
• Anand S , Lopez-VerdugoF, Sanchez-GarciaJet al. Longitudinal variance of donor-derived cell-free DNA (dd-cfDNA) in stable kidney transplant (KTx) patients are influenced by donor/recipient variables. Clin. Transplant.35(9), e14395 (2021).
   PubMed Web of Science ®Google Scholar
• De Vlaminck I , ValantineHA, SnyderTMet al. Circulating cell-free DNA enables noninvasive diagnosis of heart transplant rejection. Sci. Transl. Med.6(241), 241ra277 (2014).
   Web of Science ®Google Scholar
• De Vlaminck I , MartinL, KerteszMet al. Noninvasive monitoring of infection and rejection after lung transplantation. Proc. Natl Acad. Sci. USA112(43), 13336–13341 (2015).
   PubMed Web of Science ®Google Scholar
• Zhao D , ZhouT, LuoYet al. Preliminary clinical experience applying donor-derived cell-free DNA to discern rejection in pediatric liver transplant recipients. Sci. Rep.11(1), 1138 (2021).
   PubMed Web of Science ®Google Scholar
• Zangwill SD , KindelSJ, RagalieWSet al. Early changes in cell-free DNA levels in newly transplanted heart transplant patients. Pediatr. Transplant24(1), e13622 (2020).
   PubMed Web of Science ®Google Scholar
• Beck J , BierauS, BalzerSet al. Digital droplet PCR for rapid quantification of donor DNA in the circulation of transplant recipients as a potential universal biomarker of graft injury. Clin. Chem.59(12), 1732–1741 (2013).
   PubMed Web of Science ®Google Scholar
• Beck J , OellerichM, SchutzE. A Universal droplet digital PCR approach for monitoring of graft health after transplantation using a preselected SNP set. Methods Mol. Biol.1768, 335–348 (2018).
   PubMedGoogle Scholar
• Dauber EM , KollmannD, KozakowskiNet al. Quantitative PCR of INDELs to measure donor-derived cell-free DNA-a potential method to detect acute rejection in kidney transplantation: a pilot study. Transpl. Int.33(3), 298–309 (2020).
   PubMed Web of Science ®Google Scholar
• Garcia Moreira V , PrietoGarcia B, BaltarMartin JM, OrtegaSuarez F, AlvarezFV. Cell-free DNA as a noninvasive acute rejection marker in renal transplantation. Clin. Chem.55(11), 1958–1966 (2009).
   PubMed Web of Science ®Google Scholar
• Huggett JF , CowenS, FoyCA. Considerations for digital PCR as an accurate molecular diagnostic tool. Clin. Chem.61(1), 79–88 (2015).
   PubMed Web of Science ®Google Scholar
• Jylhava J , KotipeltoT, RaitalaA, JylhaM, HervonenA, HurmeM. Aging is associated with quantitative and qualitative changes in circulating cell-free DNA: the Vitality 90+ study. Mech. Ageing Dev.132(1–2), 20–26 (2011).
   PubMed Web of Science ®Google Scholar
• Sureshkumar KK , AramadaHR, ChopraB. Impact of body mass index and recipient age on baseline donor-derived cell free DNA (dd-cfDNA) in kidney transplant recipients. Clin. Transplant34(12), e14101 (2020).
   PubMed Web of Science ®Google Scholar
• Haller N , TugS, BreitbachS, JorgensenA, SimonP. Increases in circulating cell-free DNA during aerobic running depend on intensity and duration. Int. J. Sports Physiol. Perform12(4), 455–462 (2017).
   PubMed Web of Science ®Google Scholar
• Madsen AT , HojbjergJA, SorensenBS, Winther-LarsenA. Day-to-day and within-day biological variation of cell-free DNA. EBioMedicine49, 284–290 (2019).
   PubMed Web of Science ®Google Scholar
• Hou YQ , LiangDY, LouXL, ZhangM, ZhangZH, ZhangLR. Branched DNA-based Alu quantitative assay for cell-free plasma DNA levels in patients with sepsis or systemic inflammatory response syndrome. J. Crit. Care31(1), 90–95 (2016).
   PubMed Web of Science ®Google Scholar
• Nawroz H , KochW, AnkerP, StrounM, SidranskyD. Microsatellite alterations in serum DNA of head and neck cancer patients. Nat. Med.2(9), 1035–1037 (1996).
   PubMed Web of Science ®Google Scholar
• Yamauchi M , UrabeY, OnoA, MikiD, OchiH, ChayamaK. Serial profiling of circulating tumor DNA for optimization of anti-VEGF chemotherapy in metastatic colorectal cancer patients. Int. J. Cancer142(7), 1418–1426 (2018).
   PubMed Web of Science ®Google Scholar
• Atamaniuk J , RuzickaK, StuhlmeierKM, KarimiA, EignerM, MuellerMM. Cell-free plasma DNA: a marker for apoptosis during hemodialysis. Clin. Chem.52(3), 523–526 (2006).
   PubMed Web of Science ®Google Scholar
• Xie J , YangJ, HuP. Correlations of circulating cell-free DNA with clinical manifestations in acute myocardial infarction. Am. J. Med. Sci.356(2), 121–129 (2018).
   PubMed Web of Science ®Google Scholar
• Snyder TM , KhushKK, ValantineHA, QuakeSR. Universal noninvasive detection of solid organ transplant rejection. Proc. Natl Acad. Sci. USA108(15), 6229–6234 (2011).
   PubMed Web of Science ®Google Scholar
• Lui YY , WooKS, WangAYet al. Origin of plasma cell-free DNA after solid organ transplantation. Clin. Chem.49(3), 495–496 (2003).
   PubMed Web of Science ®Google Scholar
• Macher HC , Suarez-ArtachoG, GuerreroJMet al. Monitoring of transplanted liver health by quantification of organ-specific genomic marker in circulating DNA from receptor. PLoS ONE9(12), e113987 (2014).
   PubMed Web of Science ®Google Scholar
• Zou J , DuffyB, SladeMet al. Rapid detection of donor cell free DNA in lung transplant recipients with rejections using donor-recipient HLA mismatch. Hum. Immunol.78(4), 342–349 (2017).
   PubMed Web of Science ®Google Scholar
• Gadi VK , NelsonJL, BoespflugND, GuthrieKA, KuhrCS. Soluble donor DNA concentrations in recipient serum correlate with pancreas-kidney rejection. Clin. Chem.52(3), 379–382 (2006).
   PubMed Web of Science ®Google Scholar
• Genomes Project C , AutonA, BrooksLDet al. A global reference for human genetic variation. Nature526(7571), 68–74 (2015).
   PubMed Web of Science ®Google Scholar
• Sigdel TK , VitaloneMJ, TranTQet al. A rapid noninvasive assay for the detection of renal transplant injury. Transplantation96(1), 97–101 (2013).
   PubMed Web of Science ®Google Scholar
• Hidestrand M , Tomita-MitchellA, HidestrandPMet al. Highly sensitive noninvasive cardiac transplant rejection monitoring using targeted quantification of donor-specific cell-free deoxyribonucleic acid. J. Am. Coll. Cardiol.63(12), 1224–1226 (2014).
   PubMed Web of Science ®Google Scholar
• Dengu F . Next-generation sequencing methods to detect donor-derived cell-free DNA after transplantation. Transplant Rev (Orlando)34(3), 100542 (2020).
   PubMedGoogle Scholar
• Huang E , SethiS, PengAet al. Early clinical experience using donor-derived cell-free DNA to detect rejection in kidney transplant recipients. Am. J. Transplant19(6), 1663–1670 (2019).
   PubMed Web of Science ®Google Scholar
• Khush KK , PatelJ, PinneySet al. Noninvasive detection of graft injury after heart transplant using donor-derived cell-free DNA: a prospective multicenter study. Am. J. Transplant19(10), 2889–2899 (2019).
   PubMed Web of Science ®Google Scholar
• Khush KK , DeVlaminck I, LuikartH, RossDJ, NicollsMR. Donor-derived, cell-free DNA levels by next-generation targeted sequencing are elevated in allograft rejection after lung transplantation. ERJ Open Res.7(1), 00462–2020 (2021).
   PubMedGoogle Scholar
• Puliyanda DP , SwinfordR, PizzoH, GarrisonJ, DeGolovine AM, JordanSC. Donor-derived cell-free DNA (dd-cfDNA) for detection of allograft rejection in pediatric kidney transplants. Pediatr. Transplant25(2), e13850 (2021).
   PubMed Web of Science ®Google Scholar
• Sayah D , WeigtSS, RamseyA, ArdehaliA, GoldenJ, RossDJ. Plasma donor-derived cell-free DNA levels are increased during acute cellular rejection after lung transplant: pilot data. Transplant Direct6(10), e608 (2020).
   PubMed Web of Science ®Google Scholar
• Levine DJ , RossDJ, SakoE. Single center “snapshot” experience with donor-derived cell-free DNA after lung transplantation. Biomark Insights15, 1177271920958704 (2020).
   Web of Science ®Google Scholar
• Dar P , CurnowKJ, GrossSJet al. Clinical experience and follow-up with large scale single-nucleotide polymorphism-based noninvasive prenatal aneuploidy testing. Am. J. Obstet. Gynecol.211(5), 527 e521–527 e517 (2014).
   Web of Science ®Google Scholar
• Altug Y , LiangN, RamRet al. Analytical validation of a single-nucleotide polymorphism-based donor-derived cell-free DNA assay for detecting rejection in kidney transplant patients. Transplantation103(12), 2657–2665 (2019).
   PubMed Web of Science ®Google Scholar
• Puttarajappa CM , MehtaRB, RobertsMS, SmithKJ, HariharanS. Economic analysis of screening for subclinical rejection in kidney transplantation using protocol biopsies and noninvasive biomarkers. Am. J. Transplant21(1), 186–197 (2021).
   PubMed Web of Science ®Google Scholar
• Puttarajappa CM , MehtaRB, HariharanS. Author response to comments on economic analysis of subclinical rejection screening in kidney transplantation. Am. J. Transplant21(3), 1348–1349 (2021).
   PubMed Web of Science ®Google Scholar
• Oellerich M , SherwoodK, KeownPet al. Liquid biopsies: donor-derived cell-free DNA for the detection of kidney allograft injury. Nat. Rev. Nephrol.17(9), 591–603 (2021).
   PubMed Web of Science ®Google Scholar
• Gielis EM , LedeganckKJ, DendoovenAet al. The use of plasma donor-derived, cell-free DNA to monitor acute rejection after kidney transplantation. Nephrol. Dial. Transplant.35(4), 714–721 (2020).
   PubMed Web of Science ®Google Scholar
• Zhang H , ZhengC, LiXet al. Diagnostic performance of donor-derived plasma cell-free DNA fraction for antibody-mediated rejection in post-renal transplant recipients: a prospective observational study. Front Immunol.11, 342 (2020).
   PubMed Web of Science ®Google Scholar
• Oellerich M , ChristensonRH, BeckJet al. Donor-derived cell-free DNA testing in solid organ transplantation: a value proposition. J. Appl. Lab Med.5(5), 993–1004 (2020).
   PubMedGoogle Scholar
• Ragalie WS , StammK, MahnkeDet al. Noninvasive assay for donor fraction of cell-free DNA in pediatric heart transplant recipients. J. Am. Coll. Cardiol.71(25), 2982–2983 (2018).
   PubMed Web of Science ®Google Scholar
• Richmond ME , ZangwillSD, KindelSJet al. Donor fraction cell-free DNA and rejection in adult and pediatric heart transplantation. J. Heart Lung Transplant.39(5), 454–463 (2020).
   PubMed Web of Science ®Google Scholar
• Schutz E , FischerA, BeckJet al. Graft-derived cell-free DNA, a noninvasive early rejection and graft damage marker in liver transplantation: a prospective, observational, multicenter cohort study. PLoS Med.14(4), e1002286 (2017).
   PubMed Web of Science ®Google Scholar
• Goh SK , DoH, TestroAet al. The measurement of donor-specific cell-free DNA identifies recipients with biopsy-proven acute rejection requiring treatment after liver transplantation. Transplant Direct5(7), e462 (2019).
   PubMed Web of Science ®Google Scholar
• Knuttgen F , BeckJ, DittrichMet al. Graft-derived cell-free DNA as a noninvasive biomarker of cardiac allograft rejection: a cohort study on clinical validity and confounding factors. Transplantation doi:10.1097/TP.0000000000003725 (2021) ( Epub ahead of print).
   Web of Science ®Google Scholar
• Dueck ME , LinR, ZayacAet al. Precision cancer monitoring using a novel, fully integrated, microfluidic array partitioning digital PCR platform. Sci. Rep.9(1), 19606 (2019).
   PubMedGoogle Scholar
• Quan PL , SauzadeM, BrouzesE. dPCR: A Technology Review. Sensors (Basel)18(4), 1271 (2018).
   PubMed Web of Science ®Google Scholar
• Whitlam JB , LingL, SkeneAet al. Diagnostic application of kidney allograft-derived absolute cell-free DNA levels during transplant dysfunction. Am. J. Transplant19(4), 1037–1049 (2019).
   PubMed Web of Science ®Google Scholar
• Oellerich M , ShipkovaM, AsendorfTet al. Absolute quantification of donor-derived cell-free DNA as a marker of rejection and graft injury in kidney transplantation: results from a prospective observational study. Am. J. Transplant19(11), 3087–3099 (2019).
   PubMed Web of Science ®Google Scholar
• Xiao H , GaoF, PangQet al. Diagnostic accuracy of donor-derived cell-free DNA in renal-allograft rejection: a meta-analysis. Transplantation105(6), 1303–1310 (2021).
   PubMed Web of Science ®Google Scholar
• Wijtvliet V , PlaekeP, AbramsSet al. Donor-derived cell-free DNA as a biomarker for rejection after kidney transplantation: a systematic review and meta-analysis. Transpl. Int.33(12), 1626–1642 (2020).
   PubMed Web of Science ®Google Scholar
• Jordan SC , BunnapradistS, BrombergJSet al. Donor-derived cell-free DNA identifies antibody-mediated rejection in donor specific antibody positive kidney transplant recipients. Transplant Direct4(9), e379 (2018).
   PubMedGoogle Scholar
• Vallabhajosyula P , KorutlaL, HabertheuerAet al. Tissue-specific exosome biomarkers for noninvasively monitoring immunologic rejection of transplanted tissue. J. Clin. Invest.127(4), 1375–1391 (2017).
   PubMed Web of Science ®Google Scholar