Plasma C4d+ Endothelial Microvesicles Increase in Acute Antibody-Mediated Rejection. Issue 9 (September 2017)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Transplantation. Volume 101:Issue 9(2017)
• Publication Date: 2017-09
• Subjects: Transplantation of organs, tissues, etc -- Periodicals; Transplantation immunology -- Periodicals; 617.95
• DOI: 10.1097/TP.0000000000001572
• Languages: English
• ISSNs: 0041-1337

Abstract

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 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. Abstract : The authors report in kidney transplant recipients that C4d+ endothelial microvesicles' blood level is increased in patients with antibody-mediated rejection compared to patients without, that it is correlated with the severity of rejection and that it decreases after treatment. Supplemental digital content is available in the text.