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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
Main Authors: 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
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cited_by cdi_FETCH-LOGICAL-c562t-342d657069510a77825518f128491c0fa3542c0b4dd24584f8491289184298db3
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container_issue 8
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container_title International journal of molecular sciences
container_volume 18
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
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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 &gt;0.8770 had significantly shorter ABMR survival than that of recipients with N-glycan-negative scores. 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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 &gt;0.8770 had significantly shorter ABMR survival than that of recipients with N-glycan-negative scores. 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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 &amp; 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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 &gt;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
issn 1422-0067
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1422-0067
language eng
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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
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