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Serum Aberrant N-Glycan Profile as a Marker Associated with Early Antibody-Mediated Rejection in Patients Receiving a Living Donor Kidney Transplant
We determined if the serum -glycan profile can be used as a diagnostic marker of antibody-mediated rejection (ABMR) in living donor kidney transplant (LKTx) recipients. Glycoblotting, combined with mass spectrometry, was used to retrospectively examine -glycan levels in the postoperative sera of 197...
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Published in: | International journal of molecular sciences 2017-08, Vol.18 (8), p.1731 |
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creator | Noro, Daisuke Yoneyama, Tohru Hatakeyama, Shingo Tobisawa, Yuki Mori, Kazuyuki Hashimoto, Yasuhiro Koie, Takuya Tanaka, Masakazu Nishimura, Shin-Ichiro Sasaki, Hideo Saito, Mitsuru Harada, Hiroshi Chikaraishi, Tatsuya Ishida, Hideki Tanabe, Kazunari Satoh, Shigeru Ohyama, Chikara |
description | We determined if the serum
-glycan profile can be used as a diagnostic marker of antibody-mediated rejection (ABMR) in living donor kidney transplant (LKTx) recipients. Glycoblotting, combined with mass spectrometry, was used to retrospectively examine
-glycan levels in the postoperative sera of 197 LKTx recipients of whom 16 recipients had ABMR with or without T-cell-mediated rejection (TCMR), 40 recipients had TCMR, and 141 recipients had no adverse events. Multivariate discriminant analysis for prediction of ABMR was performed by inputting an ABMR event as an explanatory variable and sex, age, and serum N-glycan level as objective variables. The N-glycan score was calculated by multiplying the level of candidate objective variables by objective function values. The ABMR predictive performance of the N-glycan score was assessed by receiver operator characteristic curve and Kaplan-Meier curve analyses. The
-glycan score discriminated ABMR with 81.25% sensitivity, 87.85% specificity, and an area under the curve (AUC) of 0.892 that was far superior to that of preformed donor-specific antibody status (AUC, 0.761). Recipients with N-glycan-positive scores >0.8770 had significantly shorter ABMR survival than that of recipients with N-glycan-negative scores. Although the limitations of our study includ its small sample size and retrospective nature, the serum N-glycan score may contribute to prediction of ABMR. |
doi_str_mv | 10.3390/ijms18081731 |
format | article |
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-glycan profile can be used as a diagnostic marker of antibody-mediated rejection (ABMR) in living donor kidney transplant (LKTx) recipients. Glycoblotting, combined with mass spectrometry, was used to retrospectively examine
-glycan levels in the postoperative sera of 197 LKTx recipients of whom 16 recipients had ABMR with or without T-cell-mediated rejection (TCMR), 40 recipients had TCMR, and 141 recipients had no adverse events. Multivariate discriminant analysis for prediction of ABMR was performed by inputting an ABMR event as an explanatory variable and sex, age, and serum N-glycan level as objective variables. The N-glycan score was calculated by multiplying the level of candidate objective variables by objective function values. The ABMR predictive performance of the N-glycan score was assessed by receiver operator characteristic curve and Kaplan-Meier curve analyses. The
-glycan score discriminated ABMR with 81.25% sensitivity, 87.85% specificity, and an area under the curve (AUC) of 0.892 that was far superior to that of preformed donor-specific antibody status (AUC, 0.761). Recipients with N-glycan-positive scores >0.8770 had significantly shorter ABMR survival than that of recipients with N-glycan-negative scores. Although the limitations of our study includ its small sample size and retrospective nature, the serum N-glycan score may contribute to prediction of ABMR.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms18081731</identifier><identifier>PMID: 28786963</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Aberration ; Adult ; Aged ; Antibody-Dependent Cell Cytotoxicity - immunology ; antibody-mediated rejection ; biomarker ; Biomarkers ; Case-Control Studies ; Diagnostic systems ; Discriminant analysis ; Female ; Glycan ; Graft rejection ; Graft Rejection - blood ; Graft Rejection - immunology ; Humans ; Immunoglobulin Isotypes - blood ; Immunoglobulin Isotypes - immunology ; Immunoglobulins ; Kaplan-Meier Estimate ; Kidney Transplantation - adverse effects ; Kidney Transplantation - mortality ; Kidney transplants ; Kidneys ; Living Donors ; Lymphocytes T ; Male ; Mass spectrometry ; Mass spectroscopy ; Middle Aged ; N-glycan ; Polysaccharides - blood ; Rejection ; Reproducibility of Results ; ROC Curve ; Sensitivity analysis ; Time Factors ; Transplants & implants ; Young Adult</subject><ispartof>International journal of molecular sciences, 2017-08, Vol.18 (8), p.1731</ispartof><rights>Copyright MDPI AG 2017</rights><rights>2017 by the authors. 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c562t-342d657069510a77825518f128491c0fa3542c0b4dd24584f8491289184298db3</citedby><cites>FETCH-LOGICAL-c562t-342d657069510a77825518f128491c0fa3542c0b4dd24584f8491289184298db3</cites><orcidid>0000-0002-0026-4079 ; 0000-0002-1098-407X ; 0000-0002-7104-0945</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1939844814/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1939844814?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25751,27922,27923,37010,37011,44588,53789,53791,74896</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28786963$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Noro, Daisuke</creatorcontrib><creatorcontrib>Yoneyama, Tohru</creatorcontrib><creatorcontrib>Hatakeyama, Shingo</creatorcontrib><creatorcontrib>Tobisawa, Yuki</creatorcontrib><creatorcontrib>Mori, Kazuyuki</creatorcontrib><creatorcontrib>Hashimoto, Yasuhiro</creatorcontrib><creatorcontrib>Koie, Takuya</creatorcontrib><creatorcontrib>Tanaka, Masakazu</creatorcontrib><creatorcontrib>Nishimura, Shin-Ichiro</creatorcontrib><creatorcontrib>Sasaki, Hideo</creatorcontrib><creatorcontrib>Saito, Mitsuru</creatorcontrib><creatorcontrib>Harada, Hiroshi</creatorcontrib><creatorcontrib>Chikaraishi, Tatsuya</creatorcontrib><creatorcontrib>Ishida, Hideki</creatorcontrib><creatorcontrib>Tanabe, Kazunari</creatorcontrib><creatorcontrib>Satoh, Shigeru</creatorcontrib><creatorcontrib>Ohyama, Chikara</creatorcontrib><title>Serum Aberrant N-Glycan Profile as a Marker Associated with Early Antibody-Mediated Rejection in Patients Receiving a Living Donor Kidney Transplant</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>We determined if the serum
-glycan profile can be used as a diagnostic marker of antibody-mediated rejection (ABMR) in living donor kidney transplant (LKTx) recipients. Glycoblotting, combined with mass spectrometry, was used to retrospectively examine
-glycan levels in the postoperative sera of 197 LKTx recipients of whom 16 recipients had ABMR with or without T-cell-mediated rejection (TCMR), 40 recipients had TCMR, and 141 recipients had no adverse events. Multivariate discriminant analysis for prediction of ABMR was performed by inputting an ABMR event as an explanatory variable and sex, age, and serum N-glycan level as objective variables. The N-glycan score was calculated by multiplying the level of candidate objective variables by objective function values. The ABMR predictive performance of the N-glycan score was assessed by receiver operator characteristic curve and Kaplan-Meier curve analyses. The
-glycan score discriminated ABMR with 81.25% sensitivity, 87.85% specificity, and an area under the curve (AUC) of 0.892 that was far superior to that of preformed donor-specific antibody status (AUC, 0.761). Recipients with N-glycan-positive scores >0.8770 had significantly shorter ABMR survival than that of recipients with N-glycan-negative scores. Although the limitations of our study includ its small sample size and retrospective nature, the serum N-glycan score may contribute to prediction of ABMR.</description><subject>Aberration</subject><subject>Adult</subject><subject>Aged</subject><subject>Antibody-Dependent Cell Cytotoxicity - immunology</subject><subject>antibody-mediated rejection</subject><subject>biomarker</subject><subject>Biomarkers</subject><subject>Case-Control Studies</subject><subject>Diagnostic systems</subject><subject>Discriminant analysis</subject><subject>Female</subject><subject>Glycan</subject><subject>Graft rejection</subject><subject>Graft Rejection - blood</subject><subject>Graft Rejection - immunology</subject><subject>Humans</subject><subject>Immunoglobulin Isotypes - blood</subject><subject>Immunoglobulin Isotypes - immunology</subject><subject>Immunoglobulins</subject><subject>Kaplan-Meier Estimate</subject><subject>Kidney Transplantation - adverse effects</subject><subject>Kidney Transplantation - mortality</subject><subject>Kidney transplants</subject><subject>Kidneys</subject><subject>Living Donors</subject><subject>Lymphocytes T</subject><subject>Male</subject><subject>Mass spectrometry</subject><subject>Mass spectroscopy</subject><subject>Middle Aged</subject><subject>N-glycan</subject><subject>Polysaccharides - blood</subject><subject>Rejection</subject><subject>Reproducibility of Results</subject><subject>ROC Curve</subject><subject>Sensitivity analysis</subject><subject>Time Factors</subject><subject>Transplants & implants</subject><subject>Young Adult</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNpdkk1v1DAQQCMEoqVw44wsceFAwN9xLkirUkrFFhCUs-U4k61D1t7aSVH-Bz8Yl5Rqy8UezTw9zYymKJ4T_IaxGr91_TYRhRWpGHlQHBJOaYmxrB7uxQfFk5R6jCmjon5cHFBVKVlLdlj8_g5x2qJVAzEaP6LP5ekwW-PR1xg6NwAyCRl0buJPiGiVUrDOjNCiX268RCcmDjNa-dE1oZ3Lc2iX4jfowY4ueOSyyIwO_Jhy1oK7dn6ThesleB98iOiTaz3M6CI3kHZD7uJp8agzQ4Jnt_9R8ePDycXxx3L95fTseLUurZB0LBmnrRQVlrUg2FSVokIQ1RGqeE0s7gwTnFrc8LalXCje3eSpqonitFZtw46Ks8XbBtPrXXRbE2cdjNN_EyFutImjswPoRpBGSAFAG84NBYUJNSBkfiU0XGTXu8W1m5ottDaPHM1wT3q_4t2l3oRrLUSlCCVZ8OpWEMPVBGnUW5csDHkhEKakSU0rhqXiMqMv_0P7MEWfV5UpVivOFeGZer1QNoaUInR3zRCsb05H759Oxl_sD3AH_7sV9gdgR77w</recordid><startdate>20170808</startdate><enddate>20170808</enddate><creator>Noro, Daisuke</creator><creator>Yoneyama, Tohru</creator><creator>Hatakeyama, Shingo</creator><creator>Tobisawa, Yuki</creator><creator>Mori, Kazuyuki</creator><creator>Hashimoto, Yasuhiro</creator><creator>Koie, Takuya</creator><creator>Tanaka, Masakazu</creator><creator>Nishimura, Shin-Ichiro</creator><creator>Sasaki, Hideo</creator><creator>Saito, Mitsuru</creator><creator>Harada, Hiroshi</creator><creator>Chikaraishi, Tatsuya</creator><creator>Ishida, Hideki</creator><creator>Tanabe, Kazunari</creator><creator>Satoh, Shigeru</creator><creator>Ohyama, Chikara</creator><general>MDPI AG</general><general>MDPI</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-0026-4079</orcidid><orcidid>https://orcid.org/0000-0002-1098-407X</orcidid><orcidid>https://orcid.org/0000-0002-7104-0945</orcidid></search><sort><creationdate>20170808</creationdate><title>Serum Aberrant N-Glycan Profile as a Marker Associated with Early Antibody-Mediated Rejection in Patients Receiving a Living Donor Kidney Transplant</title><author>Noro, Daisuke ; Yoneyama, Tohru ; Hatakeyama, Shingo ; Tobisawa, Yuki ; Mori, Kazuyuki ; Hashimoto, Yasuhiro ; Koie, Takuya ; Tanaka, Masakazu ; Nishimura, Shin-Ichiro ; Sasaki, Hideo ; Saito, Mitsuru ; Harada, Hiroshi ; Chikaraishi, Tatsuya ; Ishida, Hideki ; Tanabe, Kazunari ; Satoh, Shigeru ; Ohyama, Chikara</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c562t-342d657069510a77825518f128491c0fa3542c0b4dd24584f8491289184298db3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Aberration</topic><topic>Adult</topic><topic>Aged</topic><topic>Antibody-Dependent Cell Cytotoxicity - immunology</topic><topic>antibody-mediated rejection</topic><topic>biomarker</topic><topic>Biomarkers</topic><topic>Case-Control Studies</topic><topic>Diagnostic systems</topic><topic>Discriminant analysis</topic><topic>Female</topic><topic>Glycan</topic><topic>Graft rejection</topic><topic>Graft Rejection - blood</topic><topic>Graft Rejection - immunology</topic><topic>Humans</topic><topic>Immunoglobulin Isotypes - blood</topic><topic>Immunoglobulin Isotypes - immunology</topic><topic>Immunoglobulins</topic><topic>Kaplan-Meier Estimate</topic><topic>Kidney Transplantation - adverse effects</topic><topic>Kidney Transplantation - mortality</topic><topic>Kidney transplants</topic><topic>Kidneys</topic><topic>Living Donors</topic><topic>Lymphocytes T</topic><topic>Male</topic><topic>Mass spectrometry</topic><topic>Mass spectroscopy</topic><topic>Middle Aged</topic><topic>N-glycan</topic><topic>Polysaccharides - blood</topic><topic>Rejection</topic><topic>Reproducibility of Results</topic><topic>ROC Curve</topic><topic>Sensitivity analysis</topic><topic>Time Factors</topic><topic>Transplants & implants</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Noro, Daisuke</creatorcontrib><creatorcontrib>Yoneyama, Tohru</creatorcontrib><creatorcontrib>Hatakeyama, Shingo</creatorcontrib><creatorcontrib>Tobisawa, Yuki</creatorcontrib><creatorcontrib>Mori, Kazuyuki</creatorcontrib><creatorcontrib>Hashimoto, Yasuhiro</creatorcontrib><creatorcontrib>Koie, Takuya</creatorcontrib><creatorcontrib>Tanaka, Masakazu</creatorcontrib><creatorcontrib>Nishimura, Shin-Ichiro</creatorcontrib><creatorcontrib>Sasaki, Hideo</creatorcontrib><creatorcontrib>Saito, Mitsuru</creatorcontrib><creatorcontrib>Harada, Hiroshi</creatorcontrib><creatorcontrib>Chikaraishi, Tatsuya</creatorcontrib><creatorcontrib>Ishida, Hideki</creatorcontrib><creatorcontrib>Tanabe, Kazunari</creatorcontrib><creatorcontrib>Satoh, Shigeru</creatorcontrib><creatorcontrib>Ohyama, Chikara</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest research library</collection><collection>Research Library (Corporate)</collection><collection>Publicly Available Content (ProQuest)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>Directory of Open Access Journals</collection><jtitle>International journal of molecular sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Noro, Daisuke</au><au>Yoneyama, Tohru</au><au>Hatakeyama, Shingo</au><au>Tobisawa, Yuki</au><au>Mori, Kazuyuki</au><au>Hashimoto, Yasuhiro</au><au>Koie, Takuya</au><au>Tanaka, Masakazu</au><au>Nishimura, Shin-Ichiro</au><au>Sasaki, Hideo</au><au>Saito, Mitsuru</au><au>Harada, Hiroshi</au><au>Chikaraishi, Tatsuya</au><au>Ishida, Hideki</au><au>Tanabe, Kazunari</au><au>Satoh, Shigeru</au><au>Ohyama, Chikara</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Serum Aberrant N-Glycan Profile as a Marker Associated with Early Antibody-Mediated Rejection in Patients Receiving a Living Donor Kidney Transplant</atitle><jtitle>International journal of molecular sciences</jtitle><addtitle>Int J Mol Sci</addtitle><date>2017-08-08</date><risdate>2017</risdate><volume>18</volume><issue>8</issue><spage>1731</spage><pages>1731-</pages><issn>1422-0067</issn><issn>1661-6596</issn><eissn>1422-0067</eissn><abstract>We determined if the serum
-glycan profile can be used as a diagnostic marker of antibody-mediated rejection (ABMR) in living donor kidney transplant (LKTx) recipients. Glycoblotting, combined with mass spectrometry, was used to retrospectively examine
-glycan levels in the postoperative sera of 197 LKTx recipients of whom 16 recipients had ABMR with or without T-cell-mediated rejection (TCMR), 40 recipients had TCMR, and 141 recipients had no adverse events. Multivariate discriminant analysis for prediction of ABMR was performed by inputting an ABMR event as an explanatory variable and sex, age, and serum N-glycan level as objective variables. The N-glycan score was calculated by multiplying the level of candidate objective variables by objective function values. The ABMR predictive performance of the N-glycan score was assessed by receiver operator characteristic curve and Kaplan-Meier curve analyses. The
-glycan score discriminated ABMR with 81.25% sensitivity, 87.85% specificity, and an area under the curve (AUC) of 0.892 that was far superior to that of preformed donor-specific antibody status (AUC, 0.761). Recipients with N-glycan-positive scores >0.8770 had significantly shorter ABMR survival than that of recipients with N-glycan-negative scores. Although the limitations of our study includ its small sample size and retrospective nature, the serum N-glycan score may contribute to prediction of ABMR.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>28786963</pmid><doi>10.3390/ijms18081731</doi><orcidid>https://orcid.org/0000-0002-0026-4079</orcidid><orcidid>https://orcid.org/0000-0002-1098-407X</orcidid><orcidid>https://orcid.org/0000-0002-7104-0945</orcidid><oa>free_for_read</oa></addata></record> |
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ispartof | International journal of molecular sciences, 2017-08, Vol.18 (8), p.1731 |
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source | Publicly Available Content (ProQuest); PubMed Central |
subjects | Aberration Adult Aged Antibody-Dependent Cell Cytotoxicity - immunology antibody-mediated rejection biomarker Biomarkers Case-Control Studies Diagnostic systems Discriminant analysis Female Glycan Graft rejection Graft Rejection - blood Graft Rejection - immunology Humans Immunoglobulin Isotypes - blood Immunoglobulin Isotypes - immunology Immunoglobulins Kaplan-Meier Estimate Kidney Transplantation - adverse effects Kidney Transplantation - mortality Kidney transplants Kidneys Living Donors Lymphocytes T Male Mass spectrometry Mass spectroscopy Middle Aged N-glycan Polysaccharides - blood Rejection Reproducibility of Results ROC Curve Sensitivity analysis Time Factors Transplants & implants Young Adult |
title | Serum Aberrant N-Glycan Profile as a Marker Associated with Early Antibody-Mediated Rejection in Patients Receiving a Living Donor Kidney Transplant |
url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-09T19%3A57%3A24IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_doaj_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Serum%20Aberrant%20N-Glycan%20Profile%20as%20a%20Marker%20Associated%20with%20Early%20Antibody-Mediated%20Rejection%20in%20Patients%20Receiving%20a%20Living%20Donor%20Kidney%20Transplant&rft.jtitle=International%20journal%20of%20molecular%20sciences&rft.au=Noro,%20Daisuke&rft.date=2017-08-08&rft.volume=18&rft.issue=8&rft.spage=1731&rft.pages=1731-&rft.issn=1422-0067&rft.eissn=1422-0067&rft_id=info:doi/10.3390/ijms18081731&rft_dat=%3Cproquest_doaj_%3E1939844814%3C/proquest_doaj_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c562t-342d657069510a77825518f128491c0fa3542c0b4dd24584f8491289184298db3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1939844814&rft_id=info:pmid/28786963&rfr_iscdi=true |