AustralieFrV1, Main, Merge, bibRecord, 004F55

Molecular Diagnosis of Antibody-Mediated Rejection in Human Kidney Transplants

Identifieur interne : 004F55 ( Main/Merge ); précédent : 004F54; suivant : 004F56

Molecular 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.

RBID : Pascal:13-0206839

Descripteurs français

Pascal (Inist)
- Biologie moléculaire, Anticorps, Rejet, Homotransplantation, Greffon, Homme, Rein, Traitement, Diagnostic moléculaire.
Wicri :
- topic : Homme.

English descriptors

KwdEn :
- Antibody, Graft(material), Homotransplantation, Human, Kidney, Molecular biology, Molecular diagnostic, Rejection, Treatment.

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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Pascal:13-0206839

Le document en format XML

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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Molecular Diagnosis of Antibody-Mediated Rejection in Human Kidney Transplants</title>
<author><name sortKey="Sellares, J" sort="Sellares, J" uniqKey="Sellares J" first="J." last="Sellares">J. Sellares</name>
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<sZ>6 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>10 aut.</sZ>
<sZ>11 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>Alberta Transplant Applied Genomics Centre</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><inist: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>
</inist:fA14>
<country>Canada</country>
<wicri:noRegion>Edmonton, AB</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Famulski, K S" sort="Famulski, K S" uniqKey="Famulski K" first="K. S." last="Famulski">K. S. Famulski</name>
<affiliation wicri:level="1"><inist: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>
<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>10 aut.</sZ>
<sZ>11 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>Alberta Transplant Applied Genomics Centre</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><inist: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>
</inist:fA14>
<country>Canada</country>
<wicri:noRegion>Edmonton, AB</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Halloran, P F" sort="Halloran, P F" uniqKey="Halloran P" first="P. F." last="Halloran">P. F. Halloran</name>
<affiliation wicri:level="1"><inist: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>
<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>10 aut.</sZ>
<sZ>11 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>Alberta Transplant Applied Genomics Centre</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><inist: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>
</inist:fA14>
<country>Canada</country>
<wicri:noRegion>Edmonton, AB</wicri:noRegion>
</affiliation>
</author>
</analytic>
<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>
</imprint>
</series>
</biblStruct>
</sourceDesc>
<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>
</seriesStmt>
</fileDesc>
<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>
</keywords>
<keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Homme</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<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>
</TEI>
<affiliations><list><country><li>Australie</li>
<li>Canada</li>
<li>Espagne</li>
<li>France</li>
<li>Royaume-Uni</li>
<li>États-Unis</li>
</country>
<region><li>Angleterre</li>
<li>Catalogne</li>
<li>Grand Manchester</li>
<li>Île-de-France</li>
</region>
<settlement><li>Barcelone</li>
<li>Manchester</li>
<li>Paris</li>
</settlement>
</list>
<tree><country name="États-Unis"><noRegion><name sortKey="Sellares, J" sort="Sellares, J" uniqKey="Sellares J" first="J." last="Sellares">J. Sellares</name>
</noRegion>
<name sortKey="Famulski, K S" sort="Famulski, K S" uniqKey="Famulski K" first="K. S." last="Famulski">K. S. Famulski</name>
<name sortKey="Halloran, P F" sort="Halloran, P F" uniqKey="Halloran P" first="P. F." last="Halloran">P. F. Halloran</name>
<name sortKey="Hidalgo, L G" sort="Hidalgo, L G" uniqKey="Hidalgo L" first="L. G." last="Hidalgo">L. G. Hidalgo</name>
<name sortKey="Kreepala, C" sort="Kreepala, C" uniqKey="Kreepala C" first="C." last="Kreepala">C. Kreepala</name>
<name sortKey="Mengel, M" sort="Mengel, M" uniqKey="Mengel M" first="M." last="Mengel">M. Mengel</name>
<name sortKey="Reeve, J" sort="Reeve, J" uniqKey="Reeve J" first="J." last="Reeve">J. Reeve</name>
<name sortKey="Skene, A" sort="Skene, A" uniqKey="Skene A" first="A." last="Skene">A. Skene</name>
</country>
<country name="Espagne"><region name="Catalogne"><name sortKey="Sellares, J" sort="Sellares, J" uniqKey="Sellares J" first="J." last="Sellares">J. Sellares</name>
</region>
</country>
<country name="Canada"><noRegion><name sortKey="Reeve, J" sort="Reeve, J" uniqKey="Reeve J" first="J." last="Reeve">J. Reeve</name>
</noRegion>
<name sortKey="Famulski, K S" sort="Famulski, K S" uniqKey="Famulski K" first="K. S." last="Famulski">K. S. Famulski</name>
<name sortKey="Halloran, P F" sort="Halloran, P F" uniqKey="Halloran P" first="P. F." last="Halloran">P. F. Halloran</name>
<name sortKey="Hidalgo, L G" sort="Hidalgo, L G" uniqKey="Hidalgo L" first="L. G." last="Hidalgo">L. G. Hidalgo</name>
<name sortKey="Kreepala, C" sort="Kreepala, C" uniqKey="Kreepala C" first="C." last="Kreepala">C. Kreepala</name>
<name sortKey="Mengel, M" sort="Mengel, M" uniqKey="Mengel M" first="M." last="Mengel">M. Mengel</name>
<name sortKey="Sis, B" sort="Sis, B" uniqKey="Sis B" first="B." last="Sis">B. Sis</name>
</country>
<country name="France"><region name="Île-de-France"><name sortKey="Loupy, A" sort="Loupy, A" uniqKey="Loupy A" first="A." last="Loupy">A. Loupy</name>
</region>
</country>
<country name="Australie"><noRegion><name sortKey="Skene, A" sort="Skene, A" uniqKey="Skene A" first="A." last="Skene">A. Skene</name>
</noRegion>
</country>
<country name="Royaume-Uni"><region name="Angleterre"><name sortKey="De Freitas, D G" sort="De Freitas, D G" uniqKey="De Freitas D" first="D. G." last="De Freitas">D. G. De Freitas</name>
</region>
</country>
</tree>
</affiliations>
</record>

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Molecular Diagnosis of Antibody-Mediated Rejection in Human Kidney Transplants

Molecular Diagnosis of Antibody-Mediated Rejection in Human Kidney Transplants

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