Non-HLA Antibodies to Immunogenic Epitopes Predict the Evolution of Chronic Renal Allograft Injury
Chronic allograft injury (CAI) results from a humoral response to mismatches in immunogenic epitopes between the donor and recipient. Although alloantibodies against HLA antigens contribute to the pathogenesis of CAI, alloantibodies against non-HLA antigens likely contribute as well. Here, we used h...
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| Veröffentlicht in: | Journal of the American Society of Nephrology 2012-04, Vol.23 (4), p.750-763 |
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| container_title | Journal of the American Society of Nephrology |
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| creator | SIGDEL, Tara K LI LI TRAN, Tim Q KHATRI, Purvesh NAESENS, Maarten SANSANWAL, Poonam DAI, Hong HSIEH, Szu-Chuan SARWAL, Minnie M |
| description | Chronic allograft injury (CAI) results from a humoral response to mismatches in immunogenic epitopes between the donor and recipient. Although alloantibodies against HLA antigens contribute to the pathogenesis of CAI, alloantibodies against non-HLA antigens likely contribute as well. Here, we used high-density protein arrays to identify non-HLA antibodies in CAI and subsequently validated a subset in a cohort of 172 serum samples collected serially post-transplantation. There were 38 de novo non-HLA antibodies that significantly associated with the development of CAI (P80% sensitivity and 100% specificity. In conclusion, pretransplant serum levels of a defined panel of alloantibodies targeting non-HLA immunogenic antigens associate with histologic CAI in the post-transplant period. Validation in a larger, prospective transplant cohort may lead to a noninvasive method to predict and monitor for CAI. |
| doi_str_mv | 10.1681/ASN.2011060596 |
| format | Article |
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Although alloantibodies against HLA antigens contribute to the pathogenesis of CAI, alloantibodies against non-HLA antigens likely contribute as well. Here, we used high-density protein arrays to identify non-HLA antibodies in CAI and subsequently validated a subset in a cohort of 172 serum samples collected serially post-transplantation. There were 38 de novo non-HLA antibodies that significantly associated with the development of CAI (P<0.01) on protocol post-transplant biopsies, with enrichment of their corresponding antigens in the renal cortex. Baseline levels of preformed antibodies to MIG (also called CXCL9), ITAC (also called CXCL11), IFN-γ, and glial-derived neurotrophic factor positively correlated with histologic injury at 24 months. Measuring levels of these four antibodies could help clinicians predict the development of CAI with >80% sensitivity and 100% specificity. In conclusion, pretransplant serum levels of a defined panel of alloantibodies targeting non-HLA immunogenic antigens associate with histologic CAI in the post-transplant period. Validation in a larger, prospective transplant cohort may lead to a noninvasive method to predict and monitor for CAI.</description><identifier>ISSN: 1046-6673</identifier><identifier>EISSN: 1533-3450</identifier><identifier>DOI: 10.1681/ASN.2011060596</identifier><identifier>PMID: 22302197</identifier><identifier>CODEN: JASNEU</identifier><language>eng</language><publisher>Washington, DC: American Society of Nephrology</publisher><subject>Adolescent ; Adult ; Analysis of Variance ; Antibody Formation - immunology ; Biological and medical sciences ; Biomarkers - blood ; Biopsy, Needle ; Chronic Disease ; Cohort Studies ; Epitopes - immunology ; Female ; Follow-Up Studies ; Graft Rejection - immunology ; HLA Antigens - immunology ; Humans ; Immunohistochemistry ; Isoantibodies - blood ; Kidney - immunology ; Kidney - pathology ; Kidney Failure, Chronic - diagnosis ; Kidney Failure, Chronic - surgery ; Kidney Transplantation - adverse effects ; Kidney Transplantation - immunology ; Kidneys ; Male ; Medical sciences ; Middle Aged ; Nephrology. Urinary tract diseases ; Predictive Value of Tests ; Prospective Studies ; Risk Assessment ; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases ; Surgery of the urinary system ; Transplantation, Homologous - adverse effects ; Transplantation, Homologous - immunology ; Urinary system involvement in other diseases. Miscellaneous ; Young Adult</subject><ispartof>Journal of the American Society of Nephrology, 2012-04, Vol.23 (4), p.750-763</ispartof><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c409t-92ff57e878c6198cf9bec40da98bfa114d9c50798bf709283751bf921c623bf63</citedby><cites>FETCH-LOGICAL-c409t-92ff57e878c6198cf9bec40da98bfa114d9c50798bf709283751bf921c623bf63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=25761994$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22302197$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>SIGDEL, Tara K</creatorcontrib><creatorcontrib>LI LI</creatorcontrib><creatorcontrib>TRAN, Tim Q</creatorcontrib><creatorcontrib>KHATRI, Purvesh</creatorcontrib><creatorcontrib>NAESENS, Maarten</creatorcontrib><creatorcontrib>SANSANWAL, Poonam</creatorcontrib><creatorcontrib>DAI, Hong</creatorcontrib><creatorcontrib>HSIEH, Szu-Chuan</creatorcontrib><creatorcontrib>SARWAL, Minnie M</creatorcontrib><title>Non-HLA Antibodies to Immunogenic Epitopes Predict the Evolution of Chronic Renal Allograft Injury</title><title>Journal of the American Society of Nephrology</title><addtitle>J Am Soc Nephrol</addtitle><description>Chronic allograft injury (CAI) results from a humoral response to mismatches in immunogenic epitopes between the donor and recipient. Although alloantibodies against HLA antigens contribute to the pathogenesis of CAI, alloantibodies against non-HLA antigens likely contribute as well. Here, we used high-density protein arrays to identify non-HLA antibodies in CAI and subsequently validated a subset in a cohort of 172 serum samples collected serially post-transplantation. There were 38 de novo non-HLA antibodies that significantly associated with the development of CAI (P<0.01) on protocol post-transplant biopsies, with enrichment of their corresponding antigens in the renal cortex. Baseline levels of preformed antibodies to MIG (also called CXCL9), ITAC (also called CXCL11), IFN-γ, and glial-derived neurotrophic factor positively correlated with histologic injury at 24 months. Measuring levels of these four antibodies could help clinicians predict the development of CAI with >80% sensitivity and 100% specificity. In conclusion, pretransplant serum levels of a defined panel of alloantibodies targeting non-HLA immunogenic antigens associate with histologic CAI in the post-transplant period. Validation in a larger, prospective transplant cohort may lead to a noninvasive method to predict and monitor for CAI.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Analysis of Variance</subject><subject>Antibody Formation - immunology</subject><subject>Biological and medical sciences</subject><subject>Biomarkers - blood</subject><subject>Biopsy, Needle</subject><subject>Chronic Disease</subject><subject>Cohort Studies</subject><subject>Epitopes - immunology</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Graft Rejection - immunology</subject><subject>HLA Antigens - immunology</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Isoantibodies - blood</subject><subject>Kidney - immunology</subject><subject>Kidney - pathology</subject><subject>Kidney Failure, Chronic - diagnosis</subject><subject>Kidney Failure, Chronic - surgery</subject><subject>Kidney Transplantation - adverse effects</subject><subject>Kidney Transplantation - immunology</subject><subject>Kidneys</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Nephrology. Urinary tract diseases</subject><subject>Predictive Value of Tests</subject><subject>Prospective Studies</subject><subject>Risk Assessment</subject><subject>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</subject><subject>Surgery of the urinary system</subject><subject>Transplantation, Homologous - adverse effects</subject><subject>Transplantation, Homologous - immunology</subject><subject>Urinary system involvement in other diseases. Miscellaneous</subject><subject>Young Adult</subject><issn>1046-6673</issn><issn>1533-3450</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkEtPxCAUhYnR-N66NGyMq448WijLZjLqJBM1PtYNpaCYFkagJv57mTjq6r6-e27uAeAMoxlmNb5qnu5mBGGMGKoE2wGHuKK0oGWFdnOOSlYwxukBOIrxHSFcEc73wQEhFBEs-CHo7rwrblcNbFyyne-tjjB5uBzHyflX7ayCi7VNfp37D0H3ViWY3jRcfPphStY76A2cvwW_IR-1kwNshsG_BmkSXLr3KXydgD0jh6hPt_EYvFwvnue3xer-ZjlvVoUqkUiFIMZUXNe8VgyLWhnR6Tzppag7IzEue6EqxDcVR4LUlFe4M4JgxQjtDKPH4PJHdx38x6RjakcblR4G6bSfYisYrSkuRZnJ2Q-pgo8xaNOugx1l-Goxaje2ttnW9t_WvHC-lZ66Ufd_-K-PGbjYAjIqOZggnbLxn6t4_ilf_gbovH8s</recordid><startdate>20120401</startdate><enddate>20120401</enddate><creator>SIGDEL, Tara K</creator><creator>LI LI</creator><creator>TRAN, Tim Q</creator><creator>KHATRI, Purvesh</creator><creator>NAESENS, Maarten</creator><creator>SANSANWAL, Poonam</creator><creator>DAI, Hong</creator><creator>HSIEH, Szu-Chuan</creator><creator>SARWAL, Minnie M</creator><general>American Society of Nephrology</general><scope>IQODW</scope><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>7X8</scope></search><sort><creationdate>20120401</creationdate><title>Non-HLA Antibodies to Immunogenic Epitopes Predict the Evolution of Chronic Renal Allograft Injury</title><author>SIGDEL, Tara K ; LI LI ; TRAN, Tim Q ; KHATRI, Purvesh ; NAESENS, Maarten ; SANSANWAL, Poonam ; DAI, Hong ; HSIEH, Szu-Chuan ; SARWAL, Minnie M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c409t-92ff57e878c6198cf9bec40da98bfa114d9c50798bf709283751bf921c623bf63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Analysis of Variance</topic><topic>Antibody Formation - immunology</topic><topic>Biological and medical sciences</topic><topic>Biomarkers - blood</topic><topic>Biopsy, Needle</topic><topic>Chronic Disease</topic><topic>Cohort Studies</topic><topic>Epitopes - immunology</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Graft Rejection - immunology</topic><topic>HLA Antigens - immunology</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Isoantibodies - blood</topic><topic>Kidney - immunology</topic><topic>Kidney - pathology</topic><topic>Kidney Failure, Chronic - diagnosis</topic><topic>Kidney Failure, Chronic - surgery</topic><topic>Kidney Transplantation - adverse effects</topic><topic>Kidney Transplantation - immunology</topic><topic>Kidneys</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Nephrology. Urinary tract diseases</topic><topic>Predictive Value of Tests</topic><topic>Prospective Studies</topic><topic>Risk Assessment</topic><topic>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</topic><topic>Surgery of the urinary system</topic><topic>Transplantation, Homologous - adverse effects</topic><topic>Transplantation, Homologous - immunology</topic><topic>Urinary system involvement in other diseases. Miscellaneous</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>SIGDEL, Tara K</creatorcontrib><creatorcontrib>LI LI</creatorcontrib><creatorcontrib>TRAN, Tim Q</creatorcontrib><creatorcontrib>KHATRI, Purvesh</creatorcontrib><creatorcontrib>NAESENS, Maarten</creatorcontrib><creatorcontrib>SANSANWAL, Poonam</creatorcontrib><creatorcontrib>DAI, Hong</creatorcontrib><creatorcontrib>HSIEH, Szu-Chuan</creatorcontrib><creatorcontrib>SARWAL, Minnie M</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of the American Society of Nephrology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>SIGDEL, Tara K</au><au>LI LI</au><au>TRAN, Tim Q</au><au>KHATRI, Purvesh</au><au>NAESENS, Maarten</au><au>SANSANWAL, Poonam</au><au>DAI, Hong</au><au>HSIEH, Szu-Chuan</au><au>SARWAL, Minnie M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Non-HLA Antibodies to Immunogenic Epitopes Predict the Evolution of Chronic Renal Allograft Injury</atitle><jtitle>Journal of the American Society of Nephrology</jtitle><addtitle>J Am Soc Nephrol</addtitle><date>2012-04-01</date><risdate>2012</risdate><volume>23</volume><issue>4</issue><spage>750</spage><epage>763</epage><pages>750-763</pages><issn>1046-6673</issn><eissn>1533-3450</eissn><coden>JASNEU</coden><abstract>Chronic allograft injury (CAI) results from a humoral response to mismatches in immunogenic epitopes between the donor and recipient. Although alloantibodies against HLA antigens contribute to the pathogenesis of CAI, alloantibodies against non-HLA antigens likely contribute as well. Here, we used high-density protein arrays to identify non-HLA antibodies in CAI and subsequently validated a subset in a cohort of 172 serum samples collected serially post-transplantation. There were 38 de novo non-HLA antibodies that significantly associated with the development of CAI (P<0.01) on protocol post-transplant biopsies, with enrichment of their corresponding antigens in the renal cortex. Baseline levels of preformed antibodies to MIG (also called CXCL9), ITAC (also called CXCL11), IFN-γ, and glial-derived neurotrophic factor positively correlated with histologic injury at 24 months. Measuring levels of these four antibodies could help clinicians predict the development of CAI with >80% sensitivity and 100% specificity. In conclusion, pretransplant serum levels of a defined panel of alloantibodies targeting non-HLA immunogenic antigens associate with histologic CAI in the post-transplant period. Validation in a larger, prospective transplant cohort may lead to a noninvasive method to predict and monitor for CAI.</abstract><cop>Washington, DC</cop><pub>American Society of Nephrology</pub><pmid>22302197</pmid><doi>10.1681/ASN.2011060596</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1046-6673 |
| ispartof | Journal of the American Society of Nephrology, 2012-04, Vol.23 (4), p.750-763 |
| issn | 1046-6673 1533-3450 |
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| subjects | Adolescent Adult Analysis of Variance Antibody Formation - immunology Biological and medical sciences Biomarkers - blood Biopsy, Needle Chronic Disease Cohort Studies Epitopes - immunology Female Follow-Up Studies Graft Rejection - immunology HLA Antigens - immunology Humans Immunohistochemistry Isoantibodies - blood Kidney - immunology Kidney - pathology Kidney Failure, Chronic - diagnosis Kidney Failure, Chronic - surgery Kidney Transplantation - adverse effects Kidney Transplantation - immunology Kidneys Male Medical sciences Middle Aged Nephrology. Urinary tract diseases Predictive Value of Tests Prospective Studies Risk Assessment Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases Surgery of the urinary system Transplantation, Homologous - adverse effects Transplantation, Homologous - immunology Urinary system involvement in other diseases. Miscellaneous Young Adult |
| title | Non-HLA Antibodies to Immunogenic Epitopes Predict the Evolution of Chronic Renal Allograft Injury |
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