The Molecular Landscape of Antibody‐Mediated Kidney Transplant Rejection: Evidence for NK Involvement Through CD16a Fc Receptors
The recent recognition that antibody‐mediated rejection (ABMR) is the major cause of kidney transplant loss creates strong interest in its pathogenesis. We used microarray analysis of kidney transplant biopsies to identify the changes in pure ABMR. We found that the ABMR transcript changes in the in...
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| Veröffentlicht in: | American journal of transplantation 2015-05, Vol.15 (5), p.1336-1348 |
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| creator | Venner, J. M. Hidalgo, L. G. Famulski, K. S. Chang, J. Halloran, P. F. |
| description | The recent recognition that antibody‐mediated rejection (ABMR) is the major cause of kidney transplant loss creates strong interest in its pathogenesis. We used microarray analysis of kidney transplant biopsies to identify the changes in pure ABMR. We found that the ABMR transcript changes in the initial Discovery Set were strongly conserved in a subsequent Validation Set. In the Combined Set of 703 biopsies, 2603 transcripts were significantly changed (FDR |
| doi_str_mv | 10.1111/ajt.13115 |
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The molecules that distinguish antibody‐mediated rejection of human kidney transplants from other diseases reflect CD16a Fc receptor signaling elements of NK cells and an endothelial injury‐repair response induced by cognate recognition involving antibody and CD16a.</description><identifier>ISSN: 1600-6135</identifier><identifier>EISSN: 1600-6143</identifier><identifier>DOI: 10.1111/ajt.13115</identifier><identifier>PMID: 25787894</identifier><language>eng</language><publisher>United States: Elsevier Limited</publisher><subject>Adolescent ; Adult ; Aged ; Aged, 80 and over ; Algorithms ; Antibodies - chemistry ; basic (laboratory) research / science ; Biopsy ; CD4-Positive T-Lymphocytes - cytology ; CD8-Positive T-Lymphocytes - cytology ; Chemokines ; Cohort Studies ; Cytotoxicity ; Databases, Factual ; Female ; Graft Rejection ; Human Umbilical Vein Endothelial Cells ; Humans ; Kidney Diseases - pathology ; Kidney Diseases - surgery ; Kidney Transplantation ; kidney transplantation / nephrology ; Killer Cells, Natural - cytology ; Macrophages - metabolism ; Male ; Microcirculation ; Middle Aged ; natural killer (NK) cells / NK receptors ; Receptors, IgG - metabolism ; rejection: antibody‐mediated (ABMR) ; Rodents ; signaling / signaling pathways ; Transplants & implants ; Young Adult</subject><ispartof>American journal of transplantation, 2015-05, Vol.15 (5), p.1336-1348</ispartof><rights>Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons</rights><rights>Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4545-d0d4be11957bcc6c53a954ef2f684fcac9c03d6e317a22c5176d7e0a0a1da5eb3</citedby><cites>FETCH-LOGICAL-c4545-d0d4be11957bcc6c53a954ef2f684fcac9c03d6e317a22c5176d7e0a0a1da5eb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fajt.13115$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fajt.13115$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>315,781,785,1418,27926,27927,45576,45577</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25787894$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Venner, J. M.</creatorcontrib><creatorcontrib>Hidalgo, L. G.</creatorcontrib><creatorcontrib>Famulski, K. S.</creatorcontrib><creatorcontrib>Chang, J.</creatorcontrib><creatorcontrib>Halloran, P. F.</creatorcontrib><title>The Molecular Landscape of Antibody‐Mediated Kidney Transplant Rejection: Evidence for NK Involvement Through CD16a Fc Receptors</title><title>American journal of transplantation</title><addtitle>Am J Transplant</addtitle><description>The recent recognition that antibody‐mediated rejection (ABMR) is the major cause of kidney transplant loss creates strong interest in its pathogenesis. We used microarray analysis of kidney transplant biopsies to identify the changes in pure ABMR. We found that the ABMR transcript changes in the initial Discovery Set were strongly conserved in a subsequent Validation Set. In the Combined Set of 703 biopsies, 2603 transcripts were significantly changed (FDR < 0.05) in ABMR versus all other biopsies. In cultured cells, the transcripts strongly associated with ABMR were expressed in endothelial cells, e.g. cadherins CDH5 and CDH13; IFNG‐treated endothelial cells, e.g. phospholipase PLA1A and chemokine CXCL11; or NK cells, e.g. cytotoxicity molecules granulysin (GNLY) and FGFBP2. Other ABMR transcripts were expressed in normal kidney but not cell lines, either increased e.g. Duffy chemokine receptor (DARC) or decreased e.g. sclerostin (SOST). Pathway analysis of ABMR transcripts identified angiogenesis, with roles for angiopoietin and vascular endothelial growth factors; leukocyte‐endothelial interactions; and NK signaling, including evidence for CD16a Fc receptor signaling elements shared with T cells. These data support a model of ABMR involving injury‐repair in the microcirculation induced by cognate recognition involving antibody and CD16a, triggering IFNG release and antibody‐dependent NK cell‐mediated cytotoxicity.
The molecules that distinguish antibody‐mediated rejection of human kidney transplants from other diseases reflect CD16a Fc receptor signaling elements of NK cells and an endothelial injury‐repair response induced by cognate recognition involving antibody and CD16a.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Algorithms</subject><subject>Antibodies - chemistry</subject><subject>basic (laboratory) research / science</subject><subject>Biopsy</subject><subject>CD4-Positive T-Lymphocytes - cytology</subject><subject>CD8-Positive T-Lymphocytes - cytology</subject><subject>Chemokines</subject><subject>Cohort Studies</subject><subject>Cytotoxicity</subject><subject>Databases, Factual</subject><subject>Female</subject><subject>Graft Rejection</subject><subject>Human Umbilical Vein Endothelial Cells</subject><subject>Humans</subject><subject>Kidney Diseases - pathology</subject><subject>Kidney Diseases - surgery</subject><subject>Kidney Transplantation</subject><subject>kidney transplantation / nephrology</subject><subject>Killer Cells, Natural - cytology</subject><subject>Macrophages - metabolism</subject><subject>Male</subject><subject>Microcirculation</subject><subject>Middle Aged</subject><subject>natural killer (NK) cells / NK receptors</subject><subject>Receptors, IgG - metabolism</subject><subject>rejection: antibody‐mediated (ABMR)</subject><subject>Rodents</subject><subject>signaling / signaling pathways</subject><subject>Transplants & implants</subject><subject>Young Adult</subject><issn>1600-6135</issn><issn>1600-6143</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp10ctO3DAUBmCrApVLu-AFkCU2ZTHgE8fxpLvRlFsZWqlK15Fjn3QyytjBTgbNDvEEPCNPgmEoi0r15njx-dexfkIOgJ1APKdq0Z8ABxAfyC5kjI0ySPnW-52LHbIXwoIxkMk4-Uh2EiHHcpynu-ShmCO9cS3qoVWezpQ1QasOqavpxPZN5cz66f7xBk2jejT0ujEW17TwyoauVbanv3CBum-c_UrPVo1Bq5HWztMf1_TKrly7wiVGVsy9G_7M6fQbZIqe6_hOY9c7Hz6R7Vq1AT-_zX3y-_ysmF6OZj8vrqaT2UinIhUjw0xaIUAuZKV1pgVXuUixTupsnNZa6VwzbjLkIFWSaAEyMxKZYgqMEljxffJlk9t5dztg6MtlEzS28RfohlBCJtNc5EyKSI_-oQs3eBu3e1UJ5JznUR1vlPYuBI912flmqfy6BFa-FFPGYsrXYqI9fEscqiWad_m3iQhON-CuaXH9_6Ry8r3YRD4Dk0uYfw</recordid><startdate>201505</startdate><enddate>201505</enddate><creator>Venner, J. M.</creator><creator>Hidalgo, L. G.</creator><creator>Famulski, K. S.</creator><creator>Chang, J.</creator><creator>Halloran, P. F.</creator><general>Elsevier Limited</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7T5</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope></search><sort><creationdate>201505</creationdate><title>The Molecular Landscape of Antibody‐Mediated Kidney Transplant Rejection: Evidence for NK Involvement Through CD16a Fc Receptors</title><author>Venner, J. M. ; Hidalgo, L. G. ; Famulski, K. S. ; Chang, J. ; Halloran, P. F.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4545-d0d4be11957bcc6c53a954ef2f684fcac9c03d6e317a22c5176d7e0a0a1da5eb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Algorithms</topic><topic>Antibodies - chemistry</topic><topic>basic (laboratory) research / science</topic><topic>Biopsy</topic><topic>CD4-Positive T-Lymphocytes - cytology</topic><topic>CD8-Positive T-Lymphocytes - cytology</topic><topic>Chemokines</topic><topic>Cohort Studies</topic><topic>Cytotoxicity</topic><topic>Databases, Factual</topic><topic>Female</topic><topic>Graft Rejection</topic><topic>Human Umbilical Vein Endothelial Cells</topic><topic>Humans</topic><topic>Kidney Diseases - pathology</topic><topic>Kidney Diseases - surgery</topic><topic>Kidney Transplantation</topic><topic>kidney transplantation / nephrology</topic><topic>Killer Cells, Natural - cytology</topic><topic>Macrophages - metabolism</topic><topic>Male</topic><topic>Microcirculation</topic><topic>Middle Aged</topic><topic>natural killer (NK) cells / NK receptors</topic><topic>Receptors, IgG - metabolism</topic><topic>rejection: antibody‐mediated (ABMR)</topic><topic>Rodents</topic><topic>signaling / signaling pathways</topic><topic>Transplants & implants</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Venner, J. M.</creatorcontrib><creatorcontrib>Hidalgo, L. G.</creatorcontrib><creatorcontrib>Famulski, K. S.</creatorcontrib><creatorcontrib>Chang, J.</creatorcontrib><creatorcontrib>Halloran, P. F.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>American journal of transplantation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Venner, J. M.</au><au>Hidalgo, L. G.</au><au>Famulski, K. S.</au><au>Chang, J.</au><au>Halloran, P. F.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Molecular Landscape of Antibody‐Mediated Kidney Transplant Rejection: Evidence for NK Involvement Through CD16a Fc Receptors</atitle><jtitle>American journal of transplantation</jtitle><addtitle>Am J Transplant</addtitle><date>2015-05</date><risdate>2015</risdate><volume>15</volume><issue>5</issue><spage>1336</spage><epage>1348</epage><pages>1336-1348</pages><issn>1600-6135</issn><eissn>1600-6143</eissn><abstract>The recent recognition that antibody‐mediated rejection (ABMR) is the major cause of kidney transplant loss creates strong interest in its pathogenesis. We used microarray analysis of kidney transplant biopsies to identify the changes in pure ABMR. We found that the ABMR transcript changes in the initial Discovery Set were strongly conserved in a subsequent Validation Set. In the Combined Set of 703 biopsies, 2603 transcripts were significantly changed (FDR < 0.05) in ABMR versus all other biopsies. In cultured cells, the transcripts strongly associated with ABMR were expressed in endothelial cells, e.g. cadherins CDH5 and CDH13; IFNG‐treated endothelial cells, e.g. phospholipase PLA1A and chemokine CXCL11; or NK cells, e.g. cytotoxicity molecules granulysin (GNLY) and FGFBP2. Other ABMR transcripts were expressed in normal kidney but not cell lines, either increased e.g. Duffy chemokine receptor (DARC) or decreased e.g. sclerostin (SOST). Pathway analysis of ABMR transcripts identified angiogenesis, with roles for angiopoietin and vascular endothelial growth factors; leukocyte‐endothelial interactions; and NK signaling, including evidence for CD16a Fc receptor signaling elements shared with T cells. These data support a model of ABMR involving injury‐repair in the microcirculation induced by cognate recognition involving antibody and CD16a, triggering IFNG release and antibody‐dependent NK cell‐mediated cytotoxicity.
The molecules that distinguish antibody‐mediated rejection of human kidney transplants from other diseases reflect CD16a Fc receptor signaling elements of NK cells and an endothelial injury‐repair response induced by cognate recognition involving antibody and CD16a.</abstract><cop>United States</cop><pub>Elsevier Limited</pub><pmid>25787894</pmid><doi>10.1111/ajt.13115</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adolescent Adult Aged Aged, 80 and over Algorithms Antibodies - chemistry basic (laboratory) research / science Biopsy CD4-Positive T-Lymphocytes - cytology CD8-Positive T-Lymphocytes - cytology Chemokines Cohort Studies Cytotoxicity Databases, Factual Female Graft Rejection Human Umbilical Vein Endothelial Cells Humans Kidney Diseases - pathology Kidney Diseases - surgery Kidney Transplantation kidney transplantation / nephrology Killer Cells, Natural - cytology Macrophages - metabolism Male Microcirculation Middle Aged natural killer (NK) cells / NK receptors Receptors, IgG - metabolism rejection: antibody‐mediated (ABMR) Rodents signaling / signaling pathways Transplants & implants Young Adult |
| title | The Molecular Landscape of Antibody‐Mediated Kidney Transplant Rejection: Evidence for NK Involvement Through CD16a Fc Receptors |
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