ドナー由来Cell free DNAを用いた移植腎臓器障害および免疫抑制モニタリング

「1. はじめに」抗免疫療法等の進歩により移植腎の予後は年々向上し, 生着率でみた本邦での2010~2019年における現状は術後1年で96.1/98.7%(献腎/生体), 5年で87.9/93.1%(同)と報告されているが, 一方, 移植腎廃絶の原因として拒絶反応は未だ重要な位置を占めており, 移植片拒絶は移植臓器の予後に関わる大きな要因と考えられる. 移植腎の拒絶反応をはじめとした臓器障害の指標として, 実臨床では腎機能の重症度評価の指標とされる推算糸球体濾過量(estimated glomerular filtration rate ;eGFR)を反映する血清クレアチニン(Cre)値を用い...

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Published inOrgan Biology Vol. 30; no. 1; pp. 007 - 014
Main Authors 井ノ上, 逸朗, 北村, 博司, 西郷, 健一, NGUYEN, Phuong Thanh, 青山, 博道, 圷, 尚武, 丸山, 通広, 中岡, 博史, 早野, 崇秀
Format Journal Article
LanguageJapanese
Published 一般社団法人 日本臓器保存生物医学会 2023
日本臓器保存生物医学会
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ISSN1340-5152
2188-0204
DOI10.11378/organbio.30.007

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Abstract 「1. はじめに」抗免疫療法等の進歩により移植腎の予後は年々向上し, 生着率でみた本邦での2010~2019年における現状は術後1年で96.1/98.7%(献腎/生体), 5年で87.9/93.1%(同)と報告されているが, 一方, 移植腎廃絶の原因として拒絶反応は未だ重要な位置を占めており, 移植片拒絶は移植臓器の予後に関わる大きな要因と考えられる. 移植腎の拒絶反応をはじめとした臓器障害の指標として, 実臨床では腎機能の重症度評価の指標とされる推算糸球体濾過量(estimated glomerular filtration rate ;eGFR)を反映する血清クレアチニン(Cre)値を用いるが, Cre値の上昇は様々な原因による移植腎障害を反映し拒絶反応に特異的ではない. 拒絶反応をはじめとする移植臓器障害の確定診断を得るためには, 生検という侵襲的手法に基づく病理組織診断がGold Standardとされるが移植臓器によっては不可能ですらある.
AbstractList 「1. はじめに」抗免疫療法等の進歩により移植腎の予後は年々向上し, 生着率でみた本邦での2010~2019年における現状は術後1年で96.1/98.7%(献腎/生体), 5年で87.9/93.1%(同)と報告されているが, 一方, 移植腎廃絶の原因として拒絶反応は未だ重要な位置を占めており, 移植片拒絶は移植臓器の予後に関わる大きな要因と考えられる. 移植腎の拒絶反応をはじめとした臓器障害の指標として, 実臨床では腎機能の重症度評価の指標とされる推算糸球体濾過量(estimated glomerular filtration rate ;eGFR)を反映する血清クレアチニン(Cre)値を用いるが, Cre値の上昇は様々な原因による移植腎障害を反映し拒絶反応に特異的ではない. 拒絶反応をはじめとする移植臓器障害の確定診断を得るためには, 生検という侵襲的手法に基づく病理組織診断がGold Standardとされるが移植臓器によっては不可能ですらある.
Author 青山, 博道
西郷, 健一
圷, 尚武
早野, 崇秀
丸山, 通広
中岡, 博史
北村, 博司
井ノ上, 逸朗
NGUYEN, Phuong Thanh
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国立遺伝学研究所 人類遺伝研究室
独立行政法人国立病院機構 千葉東病院 病理
山口大学医学部 システムバイオインフォマティクス講座
佐々木研究所 腫瘍ゲノム研究部
千葉大学大学院医学研究院 先端応用外科
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References 9) Beck J, Bierau S, Balzer S, Andag R, Kanzow P, Schmitz J, Gaedcke J et 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 2013;59(12) 1732-1741
5) Lui YY, Woo KS, Wang AY, Yeung CK, Li PK, Chau E, Ruygrok P, Lo YM. Origin of plasma cell-free DNA after solid organ transplantation. Clin Chem 2003;49(3):495-496.
2) Lo YM, Tein MS, Pang CC, Yeung CK, Tong KL, Hjelm NM. Presence of donor-specific DNA in plasma of kidney and liver-transplant recipients. Lancet 1998;351(9112):1329-1330.
10) Grskovic M, Hiller DJ, Eubank LA, Sninsky JJ, Christopherson C,et al. Validation of a Clinical-Grade Assay to Measure Donor-Derived Cell-Free DNA in Solid Organ Transplant Recipients. J Mol Diagn 2016;18(6):890-902.
12) Zhang H, Zheng C, Li X, Fu Q, Li J Su Q et al. Diagnostic Performance of Donor Derived Plasma Cell-Free DNA Fraction for Antibody-Mediated Rejection in Post Renal Transplant Recipients: A prospective Observation Study. Front Immunol 2020;11:342.
11) Sigdel TK, Archila FA, Constantin T, Prins SA, Liberto J, Damm I, Towfighi P, Navarro S, Kirkizlar E, Demko Z et al. Optimizing Detection of Kidney Transplant Injury by Assessment of Donor-Derived Cell-Free DNA via Massively Multiplex PCR. J Clin Med 2018;8(1):19.
18) Huang E, Sethi S, Peng A, Najjar R, Mirocha J, Haas M, Vo A, Jordan SC. Early clinical experience using donor-derived cell-free DNA to detect rejection in kidney transplant recipients. Am J Transplant 2019;19(6):1663-1670.
20) Gielis EM, Ledeganck KJ, Dendooven A, Meysman P, Beirnaert C, Laukens K, De Schrijver J et al. The use of plasma donor-derived, cell-free DNA to monitor acute rejection after kidney transplantation. Nephrol Dial Transplant. 2020;35(4):714-721.
21) De Vlaminck I, Valantine HA, Snyder TM, Strehl C, Cohen G, et al. Circulating cell freeDNA enables noninvasive diagnosis of heart transplant rejection. Sci Transl Med 2014;6:241ra77.
7) Stroun M, Lyautey J, Lederrey C, Olson-Sand A, Anker P. About the possible origin and mechanism of circulating DNA apoptosis and active DNA release. Clin Chim Acta 2001;313(1-2):139-142.
22) Oellerich M, Shipkova M, Asendorf T, Walson PD, Beck J et 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 Transplant 2019;19(11):3087-3099.
19) Xiao H, Gao F, Pang Q, Xia Q, Zeng X, Peng J, Fan L, Liu J, Wang Z, Li H. Diagnostic Accuracy of Donor-derived Cell-free DNA in Renal-allograft Rejection: A Meta-analysis. Transplantation. 2021;105(6):1303-1310.
16) Sigdel TK, Archila FA, Constantin T, Prins SA, Liberto J et al. Optimizing Detection of Kidney Transplant Injury by Assessment of Donor-Derived Cell-Free DNA via Massively Multiplex PCR. J Clin Med 2019;8:19
1) 一般社団法人日本移植学会.ファクトブック2021 http://www.asas.or.jp/jst/pdf/factbook/factbook2021.pdf
8) Fan HC, Blumenfeld YJ, Chitkara U, Hudgins L, Quake SR. Analysis of the size distribution of fetal and maternal cell-free DNA by paired-end sequencing. Clin Chem 2010;56(8):1279-1286.
15) Goh SK, Do H, Testro A, Pavlovic J et al. The Measurement of Donor-Specific Cell-Free DNA Identifies Recipients With Biopsy-Proven Acute Rejection Requiring Treatment After Liver Transplantation. Transplant Direct. 2019;5(7):e462.
3) Mandel P, Metais P. Nuclear Acids in Human Blood Plasma. C R Seances Soc Biol Fil 1948; 142 241-243
6) Giacona MB, Ruben GC, Iczkowski KA, Roos TB, Porter DM, Sorenson GD. Cell-free DNA in human blood plasma: length measurements in patients with pancreatic cancer and healthy controls. Pancreas 1998;17(1):89-97.
13) Ahmadloo S, Nakaoka H, Hayano T, Hosomichi K, Inoue I et al. Rapid and cost-effective high-throughput sequencing for identification of germline mutations of BRCA1 and BRCA2. Hum Genet 2017;62(5):561-567.
17) Thongprayoon C, Vaitla P, Craici IM, Leeaphorn N, Hansrivijit P, Salim SA, Bathini T, Cabeza Rivera FH, Cheungpasitporn W. The Use of Donor-Derived Cell-Free DNA for Assessment of Allograft Rejection and Injury Status. J Clin Med 2020;9(5):1480.
4) Lui YY, Chik KW, Chiu RW, Ho CY, Lam CW, Lo YM. Predominant hematopoietic origin of cell-free DNA in plasma and serum after sex-mismatched bone marrow transplantation. Clin Chem 2002;48(3):421-427.
14) Schutz E, Fischer A, Beck J et 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 2017 14; e1002286.
References_xml – reference: 5) Lui YY, Woo KS, Wang AY, Yeung CK, Li PK, Chau E, Ruygrok P, Lo YM. Origin of plasma cell-free DNA after solid organ transplantation. Clin Chem 2003;49(3):495-496.
– reference: 7) Stroun M, Lyautey J, Lederrey C, Olson-Sand A, Anker P. About the possible origin and mechanism of circulating DNA apoptosis and active DNA release. Clin Chim Acta 2001;313(1-2):139-142.
– reference: 17) Thongprayoon C, Vaitla P, Craici IM, Leeaphorn N, Hansrivijit P, Salim SA, Bathini T, Cabeza Rivera FH, Cheungpasitporn W. The Use of Donor-Derived Cell-Free DNA for Assessment of Allograft Rejection and Injury Status. J Clin Med 2020;9(5):1480.
– reference: 18) Huang E, Sethi S, Peng A, Najjar R, Mirocha J, Haas M, Vo A, Jordan SC. Early clinical experience using donor-derived cell-free DNA to detect rejection in kidney transplant recipients. Am J Transplant 2019;19(6):1663-1670.
– reference: 10) Grskovic M, Hiller DJ, Eubank LA, Sninsky JJ, Christopherson C,et al. Validation of a Clinical-Grade Assay to Measure Donor-Derived Cell-Free DNA in Solid Organ Transplant Recipients. J Mol Diagn 2016;18(6):890-902.
– reference: 14) Schutz E, Fischer A, Beck J et 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 2017 14; e1002286.
– reference: 21) De Vlaminck I, Valantine HA, Snyder TM, Strehl C, Cohen G, et al. Circulating cell freeDNA enables noninvasive diagnosis of heart transplant rejection. Sci Transl Med 2014;6:241ra77.
– reference: 22) Oellerich M, Shipkova M, Asendorf T, Walson PD, Beck J et 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 Transplant 2019;19(11):3087-3099.
– reference: 9) Beck J, Bierau S, Balzer S, Andag R, Kanzow P, Schmitz J, Gaedcke J et 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 2013;59(12) 1732-1741
– reference: 16) Sigdel TK, Archila FA, Constantin T, Prins SA, Liberto J et al. Optimizing Detection of Kidney Transplant Injury by Assessment of Donor-Derived Cell-Free DNA via Massively Multiplex PCR. J Clin Med 2019;8:19
– reference: 12) Zhang H, Zheng C, Li X, Fu Q, Li J Su Q et al. Diagnostic Performance of Donor Derived Plasma Cell-Free DNA Fraction for Antibody-Mediated Rejection in Post Renal Transplant Recipients: A prospective Observation Study. Front Immunol 2020;11:342.
– reference: 19) Xiao H, Gao F, Pang Q, Xia Q, Zeng X, Peng J, Fan L, Liu J, Wang Z, Li H. Diagnostic Accuracy of Donor-derived Cell-free DNA in Renal-allograft Rejection: A Meta-analysis. Transplantation. 2021;105(6):1303-1310.
– reference: 2) Lo YM, Tein MS, Pang CC, Yeung CK, Tong KL, Hjelm NM. Presence of donor-specific DNA in plasma of kidney and liver-transplant recipients. Lancet 1998;351(9112):1329-1330.
– reference: 4) Lui YY, Chik KW, Chiu RW, Ho CY, Lam CW, Lo YM. Predominant hematopoietic origin of cell-free DNA in plasma and serum after sex-mismatched bone marrow transplantation. Clin Chem 2002;48(3):421-427.
– reference: 11) Sigdel TK, Archila FA, Constantin T, Prins SA, Liberto J, Damm I, Towfighi P, Navarro S, Kirkizlar E, Demko Z et al. Optimizing Detection of Kidney Transplant Injury by Assessment of Donor-Derived Cell-Free DNA via Massively Multiplex PCR. J Clin Med 2018;8(1):19.
– reference: 3) Mandel P, Metais P. Nuclear Acids in Human Blood Plasma. C R Seances Soc Biol Fil 1948; 142 241-243
– reference: 20) Gielis EM, Ledeganck KJ, Dendooven A, Meysman P, Beirnaert C, Laukens K, De Schrijver J et al. The use of plasma donor-derived, cell-free DNA to monitor acute rejection after kidney transplantation. Nephrol Dial Transplant. 2020;35(4):714-721.
– reference: 15) Goh SK, Do H, Testro A, Pavlovic J et al. The Measurement of Donor-Specific Cell-Free DNA Identifies Recipients With Biopsy-Proven Acute Rejection Requiring Treatment After Liver Transplantation. Transplant Direct. 2019;5(7):e462.
– reference: 6) Giacona MB, Ruben GC, Iczkowski KA, Roos TB, Porter DM, Sorenson GD. Cell-free DNA in human blood plasma: length measurements in patients with pancreatic cancer and healthy controls. Pancreas 1998;17(1):89-97.
– reference: 8) Fan HC, Blumenfeld YJ, Chitkara U, Hudgins L, Quake SR. Analysis of the size distribution of fetal and maternal cell-free DNA by paired-end sequencing. Clin Chem 2010;56(8):1279-1286.
– reference: 1) 一般社団法人日本移植学会.ファクトブック2021 http://www.asas.or.jp/jst/pdf/factbook/factbook2021.pdf
– reference: 13) Ahmadloo S, Nakaoka H, Hayano T, Hosomichi K, Inoue I et al. Rapid and cost-effective high-throughput sequencing for identification of germline mutations of BRCA1 and BRCA2. Hum Genet 2017;62(5):561-567.
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Snippet 「1. はじめに」抗免疫療法等の進歩により移植腎の予後は年々向上し, 生着率でみた本邦での2010~2019年における現状は術後1年で96.1/98.7%(献腎/生体), 5年で87.9/93.1%(同)と報告されているが, 一方, 移植腎廃絶の原因として拒絶反応は未だ重要な位置を占めており,...
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jstage
SourceType Publisher
StartPage 007
SubjectTerms セルフリーDNA
一塩基多型
免疫抑制
移植臓器障害
非侵襲的モニタリング
Title ドナー由来Cell free DNAを用いた移植腎臓器障害および免疫抑制モニタリング
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