Molecular Diagnosis of Antibody-Mediated Rejection in Human Kidney Transplants
Identifieur interne : 005461 ( PascalFrancis/Curation ); précédent : 005460; suivant : 005462Molecular Diagnosis of Antibody-Mediated Rejection in Human Kidney Transplants
Auteurs : J. Sellares [États-Unis, Espagne] ; J. Reeve [États-Unis, Canada] ; A. Loupy [France] ; M. Mengel [États-Unis, Canada] ; B. Sis [Canada] ; A. Skene [États-Unis, Australie] ; D. G. De Freitas [Royaume-Uni] ; C. Kreepala [États-Unis, Canada] ; L. G. Hidalgo [États-Unis, Canada] ; K. S. Famulski [États-Unis, Canada] ; P. F. Halloran [États-Unis, Canada]Source :
- American journal of transplantation : (Print) [ 1600-6135 ] ; 2013.
Descripteurs français
- Pascal (Inist)
- Wicri :
- topic : Homme.
English descriptors
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Abstract
Antibody-mediated rejection is the major cause of kidney transplant failure, but the histology-based diagnostic system misses most cases due to its requirement for C4d positivity. We hypothesized that gene expression data could be used to test biopsies for the presence of antibody-mediated rejection. To develop a molecular test, we prospectively assigned diagnoses, including C4d-negative antibody-mediated rejection, to 403 indication biopsies from 315 patients, based on histology (microcirculation lesions) and donor-specific HLA antibody. We then used microarray data to develop classifiers that assigned antibody-mediated rejection scores to each biopsy. The transcripts distinguishing antibody-mediated rejection from other conditions were mostly expressed in endothelial cells or NK cells, or were IFNG-inducible. The scores correlated with the presence of microcirculation lesions and donor-specific antibody. Of 45 biopsies with scores >0.5, 39 had been diagnosed as antibody-mediated rejection on the basis of histology and donor-specific antibody. High scores were also associated with unanimity among pathologists that antibody-mediated rejection was present. The molecular score also strongly predicted future graft loss in Cox regression analysis. We conclude that microarray assessment of gene expression can assign a probability of ABMR to transplant biopsies without knowledge of HLA antibody status, histology, or C4d staining, and predicts future failure.
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Molecular Diagnosis of Antibody-Mediated Rejection in Human Kidney Transplants</title>
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<author><name sortKey="Famulski, K S" sort="Famulski, K S" uniqKey="Famulski K" first="K. S." last="Famulski">K. S. Famulski</name>
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<author><name sortKey="Halloran, P F" sort="Halloran, P F" uniqKey="Halloran P" first="P. F." last="Halloran">P. F. Halloran</name>
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<series><title level="j" type="main">American journal of transplantation : (Print)</title>
<title level="j" type="abbreviated">Am. j. transplant. : (Print)</title>
<idno type="ISSN">1600-6135</idno>
<imprint><date when="2013">2013</date>
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<seriesStmt><title level="j" type="main">American journal of transplantation : (Print)</title>
<title level="j" type="abbreviated">Am. j. transplant. : (Print)</title>
<idno type="ISSN">1600-6135</idno>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antibody</term>
<term>Graft(material)</term>
<term>Homotransplantation</term>
<term>Human</term>
<term>Kidney</term>
<term>Molecular biology</term>
<term>Molecular diagnostic</term>
<term>Rejection</term>
<term>Treatment</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Biologie moléculaire</term>
<term>Anticorps</term>
<term>Rejet</term>
<term>Homotransplantation</term>
<term>Greffon</term>
<term>Homme</term>
<term>Rein</term>
<term>Traitement</term>
<term>Diagnostic moléculaire</term>
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<keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Homme</term>
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<front><div type="abstract" xml:lang="en">Antibody-mediated rejection is the major cause of kidney transplant failure, but the histology-based diagnostic system misses most cases due to its requirement for C4d positivity. We hypothesized that gene expression data could be used to test biopsies for the presence of antibody-mediated rejection. To develop a molecular test, we prospectively assigned diagnoses, including C4d-negative antibody-mediated rejection, to 403 indication biopsies from 315 patients, based on histology (microcirculation lesions) and donor-specific HLA antibody. We then used microarray data to develop classifiers that assigned antibody-mediated rejection scores to each biopsy. The transcripts distinguishing antibody-mediated rejection from other conditions were mostly expressed in endothelial cells or NK cells, or were IFNG-inducible. The scores correlated with the presence of microcirculation lesions and donor-specific antibody. Of 45 biopsies with scores >0.5, 39 had been diagnosed as antibody-mediated rejection on the basis of histology and donor-specific antibody. High scores were also associated with unanimity among pathologists that antibody-mediated rejection was present. The molecular score also strongly predicted future graft loss in Cox regression analysis. We conclude that microarray assessment of gene expression can assign a probability of ABMR to transplant biopsies without knowledge of HLA antibody status, histology, or C4d staining, and predicts future failure.</div>
</front>
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<fA03 i2="1"><s0>Am. j. transplant. : (Print)</s0>
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<fA06><s2>4</s2>
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<fA08 i1="01" i2="1" l="ENG"><s1>Molecular Diagnosis of Antibody-Mediated Rejection in Human Kidney Transplants</s1>
</fA08>
<fA11 i1="01" i2="1"><s1>SELLARES (J.)</s1>
</fA11>
<fA11 i1="02" i2="1"><s1>REEVE (J.)</s1>
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<fA11 i1="03" i2="1"><s1>LOUPY (A.)</s1>
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<fA11 i1="10" i2="1"><s1>FAMULSKI (K. S.)</s1>
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<fA11 i1="11" i2="1"><s1>HALLORAN (P. F.)</s1>
</fA11>
<fA14 i1="01"><s1>Alberta Transplant Applied Genomics Centre</s1>
<s2>Edmonton, Alberta</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>6 aut.</sZ>
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<sZ>10 aut.</sZ>
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<fA14 i1="02"><s1>Servei de Nefrologia, Hospital de la Vall d'Hebron</s1>
<s2>Barcelona</s2>
<s3>ESP</s3>
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</fA14>
<fA14 i1="03"><s1>Department of Laboratory Medicine and Pathology, University of Alberta</s1>
<s2>Edmonton, AB</s2>
<s3>CAN</s3>
<sZ>2 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>10 aut.</sZ>
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<fA14 i1="04"><s1>Kidney Transplant Department, Necker Hospital</s1>
<s2>Paris</s2>
<s3>FRA</s3>
<sZ>3 aut.</sZ>
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<fA14 i1="05"><s1>Department of Anatomical Pathology, Austin Hospital</s1>
<s2>Heidelberg, Victoria</s2>
<s3>AUS</s3>
<sZ>6 aut.</sZ>
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<fA14 i1="06"><s1>Department of Renal Medicine, Manchester Royal Infirmary</s1>
<s2>Manchester</s2>
<s3>GBR</s3>
<sZ>7 aut.</sZ>
</fA14>
<fA14 i1="07"><s1>Department of Medicine, Division of Nephrology and Transplant Immunology, University of Alberta</s1>
<s2>Edmonton, AB</s2>
<s3>CAN</s3>
<sZ>8 aut.</sZ>
<sZ>11 aut.</sZ>
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<fA61><s0>A</s0>
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</fA66>
<fC01 i1="01" l="ENG"><s0>Antibody-mediated rejection is the major cause of kidney transplant failure, but the histology-based diagnostic system misses most cases due to its requirement for C4d positivity. We hypothesized that gene expression data could be used to test biopsies for the presence of antibody-mediated rejection. To develop a molecular test, we prospectively assigned diagnoses, including C4d-negative antibody-mediated rejection, to 403 indication biopsies from 315 patients, based on histology (microcirculation lesions) and donor-specific HLA antibody. We then used microarray data to develop classifiers that assigned antibody-mediated rejection scores to each biopsy. The transcripts distinguishing antibody-mediated rejection from other conditions were mostly expressed in endothelial cells or NK cells, or were IFNG-inducible. The scores correlated with the presence of microcirculation lesions and donor-specific antibody. Of 45 biopsies with scores >0.5, 39 had been diagnosed as antibody-mediated rejection on the basis of histology and donor-specific antibody. High scores were also associated with unanimity among pathologists that antibody-mediated rejection was present. The molecular score also strongly predicted future graft loss in Cox regression analysis. We conclude that microarray assessment of gene expression can assign a probability of ABMR to transplant biopsies without knowledge of HLA antibody status, histology, or C4d staining, and predicts future failure.</s0>
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<fC02 i1="01" i2="X"><s0>002B25</s0>
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<s5>01</s5>
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<s5>01</s5>
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<s5>04</s5>
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<s5>05</s5>
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<fC07 i1="03" i2="X" l="SPA"><s0>Trasplantación</s0>
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<fC07 i1="04" i2="X" l="FRE"><s0>Appareil urinaire</s0>
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