Plasma C4d+ Endothelial Microvesicles Increase in Acute Antibody-mediated Rejection

Cindy M. Tower, Morayma Reyes, Karen Nelson, Nicolae Leca, Niamh Kieran, Kimberly Muczynski, Jonathan A. Jefferson, Christopher Blosser, Aleksandra Kukla, David Maurer, Wayne Chandler, Behzad Najafian

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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 following injury. We hypothesized that since 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 (NAMR) 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 to NAMR 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.

Original languageEnglish (US)
JournalTransplantation
DOIs
StateAccepted/In press - Nov 15 2016

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Antibodies
Allografts
Healthy Volunteers
Biopsy
Transplants
Kidney
Annexin A5
Wounds and Injuries
Early Diagnosis
Therapeutics
Biomarkers
Membranes

ASJC Scopus subject areas

  • Transplantation

Cite this

Tower, C. M., Reyes, M., Nelson, K., Leca, N., Kieran, N., Muczynski, K., ... Najafian, B. (Accepted/In press). Plasma C4d+ Endothelial Microvesicles Increase in Acute Antibody-mediated Rejection. Transplantation. https://doi.org/10.1097/TP.0000000000001572

Plasma C4d+ Endothelial Microvesicles Increase in Acute Antibody-mediated Rejection. / Tower, Cindy M.; Reyes, Morayma; Nelson, Karen; Leca, Nicolae; Kieran, Niamh; Muczynski, Kimberly; Jefferson, Jonathan A.; Blosser, Christopher; Kukla, Aleksandra; Maurer, David; Chandler, Wayne; Najafian, Behzad.

In: Transplantation, 15.11.2016.

Research output: Contribution to journalArticle

Tower, CM, Reyes, M, Nelson, K, Leca, N, Kieran, N, Muczynski, K, Jefferson, JA, Blosser, C, Kukla, A, Maurer, D, Chandler, W & Najafian, B 2016, 'Plasma C4d+ Endothelial Microvesicles Increase in Acute Antibody-mediated Rejection', Transplantation. https://doi.org/10.1097/TP.0000000000001572
Tower, Cindy M. ; Reyes, Morayma ; Nelson, Karen ; Leca, Nicolae ; Kieran, Niamh ; Muczynski, Kimberly ; Jefferson, Jonathan A. ; Blosser, Christopher ; Kukla, Aleksandra ; Maurer, David ; Chandler, Wayne ; Najafian, Behzad. / Plasma C4d+ Endothelial Microvesicles Increase in Acute Antibody-mediated Rejection. In: Transplantation. 2016.
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abstract = "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 following injury. We hypothesized that since 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 (NAMR) 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 to NAMR 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.",
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AU - Tower, Cindy M.

AU - Reyes, Morayma

AU - Nelson, Karen

AU - Leca, Nicolae

AU - Kieran, Niamh

AU - Muczynski, Kimberly

AU - Jefferson, Jonathan A.

AU - Blosser, Christopher

AU - Kukla, Aleksandra

AU - Maurer, David

AU - Chandler, Wayne

AU - Najafian, Behzad

PY - 2016/11/15

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N2 - 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 following injury. We hypothesized that since 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 (NAMR) 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 to NAMR 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.

AB - 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 following injury. We hypothesized that since 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 (NAMR) 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 to NAMR 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.

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