title: Reclassification of C4d-Positive Endomyocardial Biopsy (EMB) According to New International Society for Heart and Lung Transplantation (ISHLT) 2013 Categories for Reporting Pathologic Antibody-Mediated Rejection (pAMR): Preliminary Data from a Polish Single-Center Study.
abstract: BACKGROUND
  The International Society for Heart and Lung Transplantation (ISHLT) has recently proposed a new protocol for reporting pathologic diagnosis of antibody-mediated rejection (pAMR). The new criteria precisely defined antibody panels and morphologic features indicative of AMR. The aim of this study was to reclassify endomyocardial biopsy specimens (EMBs) that had previously been classified as C4d-positive (AMR1) according to the former ISHLT 2004 protocol and to verify whether the new, stricter criteria have any impact on number of AMR diagnosis.
  
  
  METHODS
  We retrospectively analyzed 1374 EMBs from 212 patients who underwent heart transplantation in the years 2001-2013 and who were diagnosed at the Department of Pathology, The Children's Memorial Health Institute. Recorded data were: histopathologic features indicative of AMR (endothelial swelling, interstitial edema, intracapillary macrophages and leucocytes); C4d stain patterns, and presence of cellular rejection (ACR) or Quilty effect in any biopsy. All EMBs were reevaluated according to new ISHLT 2013 criteria and pAMR was specified.
  
  
  RESULTS
  There were 77 EMBs from 46 (21.69%) patients that were initially diagnosed as AMR1 based on any C4d-positive stain. After reclassification according to ISHLT 2013: 22 (28.57%) EMBs were evaluated as pAMR 1(H+); 14 (18.18%) EMBs were pAMR 1(I+); 13 (16.88%) EMBs were pAMR 2, and 28 (36.36%) EMBs were pAMR0. Endothelial swelling was observed in 45 (58.44%) EMBs; interstitial edema in 32 (41.55%) EMBs, and intracapillary activated mononuclear cells in 26 (33.77%) EMBs. Then, all 1374 EMBs from 212 patients were reclassified and we noticed that pAMR1H+ was found in 95 (44.81%) patients; pAMR1I+ in 12 (5.66%) patients; pAMR2 in 8 (3.77%) patients; pAMR0 in 95 (45.75%) in patients, and pAMR3 was not present.
  
  
  CONCLUSIONS
  New, more restrictive ISHLT 2013 criteria for reporting pathologic antibody-mediated rejection (pAMR) decrease number of AMR diagnosis in a selected Polish population, but they increase number of silent/sub-silent AMR diagnoses.
authors.affiliation: Department of Pathology, Children's Memorial Health Institute, Warsaw, Poland.
authors.forename: Sylwia
authors.initials: S
authors.lastname: Szymańska
authors.affiliation: Department of Pathology, Children's Memorial Health Institute, Warsaw, Poland.
authors.forename: Wiesława
authors.initials: W
authors.lastname: Grajkowska
authors.affiliation: Department of Heart Failure and Transplantation, Institute of Cardiology, Warsaw, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Sobieszczańska-Małek
authors.affiliation: Department of Heart Failure and Transplantation, Institute of Cardiology, Warsaw, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Zieliński
authors.affiliation: Department of Pathology, Children's Memorial Health Institute, Warsaw, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Pronicki
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D015935:Complement C4b / Q000276:immunology*; D004487:Edema / Q000276:immunology / Q000473:pathology; D005260:Female; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology; D016027:Heart Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000276:immunology* / Q000473:pathology; D010446:Peptide Fragments / Q000276:immunology*; D011044:Poland; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d