title: Acute Cellular Rejection and C4d Positivity in Heart Transplantation : A Manifestation of Asymptomatic Antibody-Mediated Rejection?
abstract: OBJECTIVE
  The role of routine C4d staining in endomyocardial biopsy specimens is uncertain. The implications of a diagnosis of acute cellular rejection (ACR) with a positive C4d with or without any evidence of antibody-mediated rejection (AMR) are unclear. This study sought to evaluate a distinct phenotype of ACR+/C4d+ in AMR- patients.
  
  
  METHODS
  Data on C4d, ACR, and AMR were collected. Donor-specific antibody (DSA), panel-reactive antibody (PRA), flow crossmatch, and data on ACR and AMR episodes were also reviewed.
  
  
  RESULTS
  Thirty-five patients were followed. Group I with C4d+ biopsy specimens was compared with group II with C4d- biopsy specimens. ACR greater than 1R was higher in group I compared with group II (50% vs 7.4%; P = .01). Clinical suspicion of AMR, positive retrospective crossmatches, and detection of de novo DSA were also higher in group I.
  
  
  CONCLUSIONS
  Our result indicate that C4d and ACR positivity in posttransplant patients may be a harbinger of a subclinical form of asymptomatic AMR.
authors.affiliation: From the Division of Cardiology and Pathology, Rush University, Advocate Christ Medical Center, Chicago and Oak Lawn, IL. burhan_mohamedali@rush.edu.
authors.forename: Burhan
authors.initials: B
authors.lastname: Mohamedali
authors.affiliation: From the Division of Cardiology and Pathology, Rush University, Advocate Christ Medical Center, Chicago and Oak Lawn, IL.
authors.forename: Joseph
authors.initials: J
authors.lastname: Pyle
authors.affiliation: From the Division of Cardiology and Pathology, Rush University, Advocate Christ Medical Center, Chicago and Oak Lawn, IL.
authors.forename: Geetha
authors.initials: G
authors.lastname: Bhat
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000906:Antibodies / Q000276:immunology*; D058070:Asymptomatic Diseases; D001706:Biopsy; D001788:Blood Grouping and Crossmatching; D015935:Complement C4b / Q000276:immunology*; D005260:Female; D006084:Graft Rejection / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology*; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D007165:Immunosuppression Therapy; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology; D010446:Peptide Fragments / Q000276:immunology*; D012189:Retrospective Studies; D014019:Tissue Donors
chemical_list: D000906:Antibodies; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d
keywords: ACR; AMR; C4d; Cardiac transplant; EBM