2. Academic Validation
  3. Ultrasound molecular imaging of antibody-mediated rejection with CD16a-targeted probes in a complement-independent pathway

Ultrasound molecular imaging of antibody-mediated rejection with CD16a-targeted probes in a complement-independent pathway

  • Colloids Surf B Biointerfaces. 2025 Oct 9:257:115197. doi: 10.1016/j.colsurfb.2025.115197.
Jiahan Ma 1,  Jiani Qiu 1,  Jia Xu 1,  Qiaofeng Jin 1,  Yihan Chen 1,  Yuji Xie 1,  He Li 1,  Wenqian Wu 1,  Li Zhang 1,  Jing Wang 2,  Yu Xie 3,  Mingxing Xie 4
Affiliations

Affiliations

  • 1 Departmentof Ultrasound Medicine, Union Hospital, Tongji Medical College, HuazhongUniversity of Science and Technology, Wuhan, China; Hubei Province Clinical Research Center for Medical Imaging, Wuhan, China; HubeiProvince Key Laboratory of Molecular Imaging, Wuhan, China.
  • 2 Departmentof Ultrasound Medicine, Union Hospital, Tongji Medical College, HuazhongUniversity of Science and Technology, Wuhan, China; Hubei Province Clinical Research Center for Medical Imaging, Wuhan, China; HubeiProvince Key Laboratory of Molecular Imaging, Wuhan, China. Electronic address: jingwang2004@hust.edu.cn.
  • 3 Departmentof Ultrasound Medicine, Union Hospital, Tongji Medical College, HuazhongUniversity of Science and Technology, Wuhan, China; Hubei Province Clinical Research Center for Medical Imaging, Wuhan, China; HubeiProvince Key Laboratory of Molecular Imaging, Wuhan, China. Electronic address: xieyu_2019@hust.edu.cn.
  • 4 Departmentof Ultrasound Medicine, Union Hospital, Tongji Medical College, HuazhongUniversity of Science and Technology, Wuhan, China; Hubei Province Clinical Research Center for Medical Imaging, Wuhan, China; HubeiProvince Key Laboratory of Molecular Imaging, Wuhan, China. Electronic address: xiemx@hust.edu.cn.
PMID: 41076856 DOI: 10.1016/j.colsurfb.2025.115197
Abstract

Background: Antibody-mediated rejection (AMR) is a critical cause of graft dysfunction after heart transplantation. The diagnostic "gold standard" is invasive endomyocardial biopsy. More precise non-invasive methods are desirable. Ultrasound molecular imaging noninvasively detects molecular changes during disease progression. As CD16a molecules contribute specifically to AMR, we hypothesized that ultrasound molecular imaging with CD16a-targeted probes might be an effective method for AMR detection.

Methods: CD16a-targeted microbubbles (MBCD16a) were prepared as the specific probes. Cardiac AMR models were established via pre-sensitization with donor serum before transplantation. C1 esterase inhibitor (C1-INH) was administered to inhibit complement activation. Ultrasound molecular imaging was performed on day 14 post-transplantation. Histological characterization was confirmed by hematoxylin-eosin staining and immunohistochemistry.

Results: In vitro, MBCD16a adhered to CD16a molecules and natural killer cells more strongly than control microbubbles (MBcon). In all allografts, the ultrasound molecular imaging signals of MBCD16a exceeded the signals of MBcon, while there were no differences in the isografts. The signals of MBCD16a were significantly higher in the pre-sensitized allografts than those in the non-sensitized allografts and isografts. In the C1-INH-treated pre-sensitized group, the signals of MBCD16a were still significantly higher than those in the two control groups. Histology showed strong AMR as intense microvascular inflammation in pre-sensitized groups, with sparse complement deposition in the C1-INH-treated allografts. Furthermore, the signals of MBCD16a were strongly correlated with histologically-proven CD16a expression.

Conclusion: This study demonstrates that ultrasound molecular imaging with CD16a-targeted probes could serve as an effective noninvasive strategy for the monitoring of AMR, including the complement-deficient phenotype.

Keywords

Antibody-mediated rejection; CD16a; Ultrasound molecular imaging.

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