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Updated: Sep 30, 2026
Mouse Model of Alloimmune-induced Vascular Rejection and Transplant Arteriosclerosis
Published on: May 17, 2015
Plasma C4d+ Endothelial Microvesicles Increase in Acute Antibody-Mediated Rejection
Cindy M Tower1, Morayma Reyes, Karen Nelson
11 Department of Pathology, University of Washington, Seattle, WA. 2 Department of Laboratory Medicine, University of Washington, Seattle, WA. 3 Immunogenetics/HLA Laboratory, Bloodworks Northwest, Seattle, WA. 4 Department of Medicine, University of Washington, Seattle, WA. 5 Department of Medicine, University of Minnesota, Minneapolis, MN. 6 Laboratory Medicine and Pathology, Seattle Children's Hospital, Seattle, WA.
Background:
Antibody-mediated rejection (AMR) is a major cause of kidney allograft loss. Currently, AMR diagnosis relies on biopsy which is an invasive procedure. A noninvasive biomarker of acute AMR could lead to early diagnosis and treatment of this condition and improve allograft outcome. Microvesicles are membrane-bound vesicles released from the cell surface after injury. We hypothesized that because AMR is associated with allograft endothelial injury and C4d deposition, plasma microvesicles positive for endothelial (CD144) marker and C4d are increased in this condition.
Methods:
We studied microvesicle concentration in the plasma of 95 kidney transplant patients with allograft dysfunction and compared with 23 healthy volunteers. Biopsy diagnosis and scoring was performed using Banff classification.
Results:
In the 28 subjects with AMR, the density of C4d+/CD144+ microvesicles was on average 11-fold (P = 0.002) higher than transplant recipients with no AMR and 24-fold (P = 0.008) than healthy volunteers. Densities of C4d+ and C4d+/annexin V+ (C4d+/AVB+) microvesicles were also increased in AMR patients compared with no AMR and healthy subjects. C4d+/AVB+ microvesicles correlated with AMR biopsy severity. Nine patients with acute AMR that received treatment showed a mean 72% decrease (P = 0.01) in C4d+/CD144+ microvesicle concentration compared with pretreatment values.
Conclusions:
Quantification of plasma C4d+ microvesicles provides information about presence of AMR, its severity and response to treatment in transplant patients.
Insights
Plasma microvesicles positive for C4d and CD144 are elevated in antibody-mediated rejection (AMR). This finding offers a potential noninvasive biomarker for early diagnosis and monitoring of kidney transplant rejection.
Area of Science:
- Nephrology
- Immunology
- Transplant Science
Background:
- Antibody-mediated rejection (AMR) is a primary cause of kidney transplant failure.
- Current diagnostic methods for AMR, such as biopsy, are invasive.
- A noninvasive biomarker for acute AMR could enable earlier detection and treatment, improving outcomes.
Purpose of the Study:
- To investigate plasma microvesicles as potential noninvasive biomarkers for antibody-mediated rejection (AMR) in kidney transplant recipients.
- To determine if microvesicles expressing endothelial marker CD144 and C4d are elevated in AMR.
Main Methods:
- Plasma microvesicle concentrations were analyzed in 95 kidney transplant patients and 23 healthy volunteers.
- Patients were diagnosed with AMR based on biopsy and Banff classification.
- Microvesicles positive for C4d, CD144, and Annexin V were quantified.
Main Results:
- Patients with AMR showed significantly higher densities of C4d+/CD144+ microvesicles compared to those without AMR and healthy controls.
- Elevated levels of C4d+ and C4d+/Annexin V+ microvesicles were observed in AMR patients.
- A significant decrease in C4d+/CD144+ microvesicles was noted after treatment for acute AMR.
Conclusions:
- Quantification of plasma C4d+ microvesicles can indicate the presence and severity of AMR.
- Plasma microvesicle analysis shows promise as a noninvasive tool for monitoring AMR and treatment response in kidney transplant patients.
