Noninvasive quantification of granzyme B in cardiac allograft rejection using targeted ultrasound imaging

ObjectiveEndomyocardial biopsy is the gold standard method for the diagnosis of cardiac allograft rejection. However, it causes damage to the heart. In this study, we developed a noninvasive method for quantification of granzyme B (GzB) in vivo by targeted ultrasound imaging, which detects and provi...

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Main Authors: Yunjie Jin, Peng Gao, Lifei Liang, Yuhang Wang, Jiawei Li, Jiyan Wang, Jiangang Hou, Cheng Yang, Xiaolin Wang
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-06-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2023.1164183/full
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author Yunjie Jin
Yunjie Jin
Peng Gao
Lifei Liang
Lifei Liang
Yuhang Wang
Jiawei Li
Jiawei Li
Jiyan Wang
Jiyan Wang
Jiangang Hou
Cheng Yang
Cheng Yang
Cheng Yang
Xiaolin Wang
author_facet Yunjie Jin
Yunjie Jin
Peng Gao
Lifei Liang
Lifei Liang
Yuhang Wang
Jiawei Li
Jiawei Li
Jiyan Wang
Jiyan Wang
Jiangang Hou
Cheng Yang
Cheng Yang
Cheng Yang
Xiaolin Wang
author_sort Yunjie Jin
collection DOAJ
description ObjectiveEndomyocardial biopsy is the gold standard method for the diagnosis of cardiac allograft rejection. However, it causes damage to the heart. In this study, we developed a noninvasive method for quantification of granzyme B (GzB) in vivo by targeted ultrasound imaging, which detects and provides quantitative information for specific molecules, for acute rejection assessment in a murine cardiac transplantation model.MethodsMicrobubbles bearing anti-GzB antibodies (MBGzb) or isotype antibodies (MBcon) were prepared. Hearts were transplanted from C57BL/6J (allogeneic) or C3H (syngeneic) donors to C3H recipients. Target ultrasound imaging was performed on Days 2 and 5 post-transplantations. A pathologic assessment was performed. The expression of granzyme B and IL-6 in the heart was detected by Western blotting.ResultsAfter MB injection, we observed and collected data at 3 and 6 min before and after the flash pulse. Quantitative analysis revealed that the reduction in peak intensity was significantly higher in the allogeneic MBGzb group than in the allogeneic MBcon group and the isogeneic MBcon group at PODs 2 and 5. In the allogeneic groups, granzyme B and IL-6 expression levels were higher than those in the isogeneic group. In addition, more CD8 T cells and neutrophils were observed in the allogeneic groups.ConclusionUltrasound molecular imaging of granzyme B can be used as a noninvasive method for acute rejection detection after cardiac transplantation.
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spelling doaj.art-fceb71c963e94c07af099fe56d4711932023-06-26T10:24:18ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-06-011410.3389/fimmu.2023.11641831164183Noninvasive quantification of granzyme B in cardiac allograft rejection using targeted ultrasound imagingYunjie Jin0Yunjie Jin1Peng Gao2Lifei Liang3Lifei Liang4Yuhang Wang5Jiawei Li6Jiawei Li7Jiyan Wang8Jiyan Wang9Jiangang Hou10Cheng Yang11Cheng Yang12Cheng Yang13Xiaolin Wang14Shanghai Institute of Medical Imaging, Shanghai, ChinaDepartment of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, ChinaDepartment of Urology, Huashan Hospital, Fudan University, Shanghai, ChinaDepartment of Urology, Zhongshan Hospital, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Organ Transplantation, Shanghai, ChinaShanghai Medical College, Fudan University, Shanghai, ChinaDepartment of Urology, Zhongshan Hospital, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Organ Transplantation, Shanghai, ChinaDepartment of Urology, Zhongshan Hospital, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Organ Transplantation, Shanghai, ChinaDepartment of Urology, Huashan Hospital, Fudan University, Shanghai, ChinaDepartment of Urology, Zhongshan Hospital, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Organ Transplantation, Shanghai, ChinaZhangjiang Institute of Fudan University, Shanghai, ChinaShanghai Institute of Medical Imaging, Shanghai, ChinaObjectiveEndomyocardial biopsy is the gold standard method for the diagnosis of cardiac allograft rejection. However, it causes damage to the heart. In this study, we developed a noninvasive method for quantification of granzyme B (GzB) in vivo by targeted ultrasound imaging, which detects and provides quantitative information for specific molecules, for acute rejection assessment in a murine cardiac transplantation model.MethodsMicrobubbles bearing anti-GzB antibodies (MBGzb) or isotype antibodies (MBcon) were prepared. Hearts were transplanted from C57BL/6J (allogeneic) or C3H (syngeneic) donors to C3H recipients. Target ultrasound imaging was performed on Days 2 and 5 post-transplantations. A pathologic assessment was performed. The expression of granzyme B and IL-6 in the heart was detected by Western blotting.ResultsAfter MB injection, we observed and collected data at 3 and 6 min before and after the flash pulse. Quantitative analysis revealed that the reduction in peak intensity was significantly higher in the allogeneic MBGzb group than in the allogeneic MBcon group and the isogeneic MBcon group at PODs 2 and 5. In the allogeneic groups, granzyme B and IL-6 expression levels were higher than those in the isogeneic group. In addition, more CD8 T cells and neutrophils were observed in the allogeneic groups.ConclusionUltrasound molecular imaging of granzyme B can be used as a noninvasive method for acute rejection detection after cardiac transplantation.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1164183/fullcardiac transplantationultrasound imagingrejectioncontrast enhanced ultrasound (CEUS)granzyme B (GzmB)
spellingShingle Yunjie Jin
Yunjie Jin
Peng Gao
Lifei Liang
Lifei Liang
Yuhang Wang
Jiawei Li
Jiawei Li
Jiyan Wang
Jiyan Wang
Jiangang Hou
Cheng Yang
Cheng Yang
Cheng Yang
Xiaolin Wang
Noninvasive quantification of granzyme B in cardiac allograft rejection using targeted ultrasound imaging
Frontiers in Immunology
cardiac transplantation
ultrasound imaging
rejection
contrast enhanced ultrasound (CEUS)
granzyme B (GzmB)
title Noninvasive quantification of granzyme B in cardiac allograft rejection using targeted ultrasound imaging
title_full Noninvasive quantification of granzyme B in cardiac allograft rejection using targeted ultrasound imaging
title_fullStr Noninvasive quantification of granzyme B in cardiac allograft rejection using targeted ultrasound imaging
title_full_unstemmed Noninvasive quantification of granzyme B in cardiac allograft rejection using targeted ultrasound imaging
title_short Noninvasive quantification of granzyme B in cardiac allograft rejection using targeted ultrasound imaging
title_sort noninvasive quantification of granzyme b in cardiac allograft rejection using targeted ultrasound imaging
topic cardiac transplantation
ultrasound imaging
rejection
contrast enhanced ultrasound (CEUS)
granzyme B (GzmB)
url https://www.frontiersin.org/articles/10.3389/fimmu.2023.1164183/full
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