title: Intravascular macrophages in cardiac allograft biopsies for diagnosis of early and late antibody-mediated rejection.
abstract: BACKGROUND
  The aim of our study was to evaluate the role of intravascular macrophages in the diagnosis of early and late antibody-mediated rejection (AMR) on endomyocardial biopsies (EMBs).
  
  
  METHODS
  We reviewed 1,420 consecutive EMBs from 131 patients and selected 75 C4d+ EMBs. The C4d+ group was compared with a control group (66 patients) matched for age, gender, date of transplantation, follow-up, immunosuppressive regimen and primary heart disease. A total of 141 EMBs were evaluated. Immunoperoxidase staining for C4d and CD68 were performed. Post-transplant IgG anti-HLA reactivity was investigated by Luminex technology. Clinical data were also collected. Fourteen EMBs were available from 11 symptomatic AMR patients.
  
  
  RESULTS
  Of the 141 EMBs evaluated, 53 were positive for intravascular macrophages (CD68); among them, 32 were also positive for C4d (32 of 53, 60.4%). Of the 88 CD68- EMBs, 43 were also C4d+ (43 of 88, 48.9%). Of the 53 CD68+ EMBs, 30 EMBs were within the first year since transplantation (30 of 53, 57.8%), and among these 21 were also positive for C4d (21 of 30, 70.0%). In the late period, among the 23 CD68+ EMBs (23 of 53, 42.2%) 11 were also positive for C4d (11 of 23, 47.8%). In the early period, intravascular macrophages were more common in symptomatic (3 of 3, 100%) than asymptomatic (3 of 11, 27.3%) patients. Sensitivity and specificity of intravascular macrophages in predicting donor-specific antibodies (DSA) within the first year were 50.0% and 100.0%, respectively.
  
  
  CONCLUSIONS
  Intravascular macrophages predict C4d, DSA and symptoms early after transplantation; however, in the late period, they are unable to identify patients with circulating DSA, C4d and/or symptoms.
authors.affiliation: Department of Cardiac, Thoracic and Vascular Sciences, University of Padua, Padua, Italy.
authors.forename: Marny
authors.initials: M
authors.lastname: Fedrigo
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Feltrin
authors.forename: Francesca
authors.initials: F
authors.lastname: Poli
authors.forename: Anna Chiara
authors.initials: AC
authors.lastname: Frigo
authors.forename: Elena
authors.initials: E
authors.lastname: Benazzi
authors.forename: Antonio
authors.initials: A
authors.lastname: Gambino
authors.forename: Francesco
authors.initials: F
authors.lastname: Tona
authors.forename: Alida L P
authors.initials: AL
authors.lastname: Caforio
authors.forename: Chiara
authors.initials: C
authors.lastname: Castellani
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Toscano
authors.forename: Gino
authors.initials: G
authors.lastname: Gerosa
authors.forename: Gaetano
authors.initials: G
authors.lastname: Thiene
authors.forename: Annalisa
authors.initials: A
authors.lastname: Angelini
mesh_terms: D000328:Adult; D000906:Antibodies / Q000276:immunology*; D001706:Biopsy; D001808:Blood Vessels; D006084:Graft Rejection / Q000175:diagnosis* / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology* / Q000473:pathology*; D006801:Humans; D008264:Macrophages / Q000276:immunology*; D008875:Middle Aged; D012189:Retrospective Studies; D013997:Time Factors
chemical_list: D000906:Antibodies