title: Plasma C4d+ Endothelial Microvesicles Increase in Acute Antibody-Mediated Rejection.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  Quantification of plasma C4d+ microvesicles provides information about presence of AMR, its severity and response to treatment in transplant patients.
authors.affiliation: 1 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.
authors.forename: Cindy M
authors.initials: CM
authors.lastname: Tower
authors.forename: Morayma
authors.initials: M
authors.lastname: Reyes
authors.forename: Karen
authors.initials: K
authors.lastname: Nelson
authors.forename: Nicolae
authors.initials: N
authors.lastname: Leca
authors.forename: Niamh
authors.initials: N
authors.lastname: Kieran
authors.forename: Kimberly
authors.initials: K
authors.lastname: Muczynski
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Jefferson
authors.forename: Christopher
authors.initials: C
authors.lastname: Blosser
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Kukla
authors.forename: David
authors.initials: D
authors.lastname: Maurer
authors.forename: Wayne
authors.initials: W
authors.lastname: Chandler
authors.forename: Behzad
authors.initials: B
authors.lastname: Najafian
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D015820:Cadherins / Q000097:blood; D016022:Case-Control Studies; D055252:Cell-Derived Microparticles / Q000276:immunology*; D015935:Complement C4b / Q000276:immunology*; D042783:Endothelial Cells / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006084:Graft Rejection / Q000097:blood / Q000175:diagnosis / Q000276:immunology* / Q000628:therapy; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D007518:Isoantibodies / Q000097:blood / Q000276:immunology*; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood / Q000276:immunology*; D011237:Predictive Value of Tests; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015415:Biomarkers; D015820:Cadherins; D015935:Complement C4b; D006680:HLA Antigens; D007518:Isoantibodies; D010446:Peptide Fragments; D000099152:Cadherin 5; C032261:complement C4d