title: Biopsy-negative cardiac transplant rejection: etiology, diagnosis, and therapy.
abstract: OBJECTIVE
  As the frequency of cellular rejection after heart transplantation is decreasing, biopsy-negative episodes of rejection are being recognized more often. This article reviews the features of humoral rejection, which we believe is responsible for most episodes of biopsy-negative rejection. Hemodynamic compromise, in the absence of acute cellular rejection, called biopsy-negative rejection occurs in 10 to 20% of cardiac allograft recipients. These episodes of rejection are often more severe, and more difficult to treat, than classical acute cellular rejection. Histologic, immunofluorescence, and immunoperoxidase studies of endomyocardial biopsies from such patients often reveal intravascular macrophages, and immunoglobulin and complement deposition in capillaries, in the absence of lymphoid infiltrates, suggesting an antibody-mediated or humoral form of rejection.
  
  
  RESULTS
  Humoral rejection is associated with increased graft loss, accelerated transplant coronary artery disease, and increased mortality. Severely ill patients require intense therapy, which includes high-dose corticosteroids, cytolytic agents, intravenous heparin, intravenous gamma globulin, plasmapheresis, and/or antiproliferative agents.
  
  
  CONCLUSIONS
  Currently, our knowledge of the pathogenesis, diagnostic criteria, and optimal therapy for biopsy-negative rejection is incomplete, and evolving.
authors.affiliation: Department of Pathology, The David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA. mfishbein@mednet.ucla.edu
authors.forename: Michael C
authors.initials: MC
authors.lastname: Fishbein
authors.forename: Jon
authors.initials: J
authors.lastname: Kobashigawa
mesh_terms: D001706:Biopsy; D005455:Fluorescent Antibody Technique; D006084:Graft Rejection / Q000175:diagnosis / Q000209:etiology / Q000276:immunology / Q000628:therapy; D006333:Heart Failure / Q000628:therapy; D016027:Heart Transplantation / Q000009:adverse effects* / Q000276:immunology / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry; D007165:Immunosuppression Therapy