title: Increased macrophage density of cardiac allograft biopsies is associated with antibody-mediated rejection and alloantibodies to HLA antigens.
abstract: BACKGROUND
  Antibody-mediated rejection (AMR) is characterized histologically by intracapillary macrophages. Macrophage density may be an alternative method of determining inflammatory changes in AMR.
  
  
  METHODS
  We identified 118 heart transplant patients with serologic testing for HLA alloantibodies. Macrophage density was graded as 1+ (<45/mm(2)), 2+ (46-90/mm(2)), and 3+ (>90/mm(2)). Maximal macrophage density and complement staining over multiple biopsies were correlated with peak panel reactive antibodies (PRA), donor-specific antibodies (DSA), and the clinical diagnosis of AMR.
  
  
  RESULTS
  The presence of PRA correlated with macrophage score (p = 0.001). Macrophage density correlated with any DSA (p < 0.0001), class I DSA (p < 0.0001), class II DSA (p < 0.0001), and class II DQ (p < 0.0001). Nine patients had clinical AMR. Among patients with AMR, 89% had a biopsy over the period of AMR with ≥3+ macrophage density (89% sensitivity); among patients without AMR, 93% of patients had no biopsy at any time with ≥3+ macrophage density (specificity). There was perfect concordance between the scores of C4d positivity and macrophage density in 61% and only partial concordance in 20%, with complete discordance in 19% in biopsies taken during clinical episodes of AMR.
  
  
  CONCLUSIONS
  Macrophage density in allograft endomyocardial biopsies is frequently elevated during clinical episodes of AMR and correlates well with alloantibodies.
authors.affiliation: Department of Pathology and Cardiology, University of Maryland Medical Center, Baltimore, MD, USA.
authors.forename: Lauren
authors.initials: L
authors.lastname: Xu
authors.forename: Jennifer
authors.initials: J
authors.lastname: Collins
authors.forename: Cinthia
authors.initials: C
authors.lastname: Drachenberg
authors.forename: Debra
authors.initials: D
authors.lastname: Kukuruga
authors.forename: Allen
authors.initials: A
authors.lastname: Burke
mesh_terms: D000328:Adult; D064591:Allografts; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D006680:HLA Antigens / Q000276:immunology* / Q000378:metabolism; D006331:Heart Diseases / Q000150:complications* / Q000601:surgery; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D007124:Immunoenzyme Techniques; D007249:Inflammation / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D007518:Isoantibodies / Q000009:adverse effects* / Q000097:blood / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D014019:Tissue Donors
chemical_list: D006680:HLA Antigens; D007518:Isoantibodies
keywords: antibody-mediated rejection; cardiac allograft; complement; macrophages; pathology