Intravascular macrophages in cardiac allograft biopsies for diagnosis of early and late antibody-mediated rejection

Marny Fedrigo, Giuseppe Feltrin, Francesca Poli, Anna Chiara Frigo, Elena Benazzi, Antonio Gambino, Francesco Tona, Alida L P Caforio, Chiara Castellani, Giuseppe Toscano, Gino Gerosa, Gaetano Thiene, Annalisa Angelini

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)404-409
Number of pages6
JournalJournal of Heart and Lung Transplantation
Issue number4
Publication statusPublished - Apr 2013


  • anti-HLA antibodies
  • antibody-mediated rejection
  • C4d
  • heart transplantation
  • immunohistochemistry
  • intravascular macrophages

ASJC Scopus subject areas

  • Transplantation
  • Cardiology and Cardiovascular Medicine
  • Pulmonary and Respiratory Medicine
  • Surgery


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