title: Biopsy-diagnosed antibody-mediated rejection based on the proposed International Society for Heart and Lung Transplantation working formulation is associated with adverse cardiovascular outcomes after pediatric heart transplant.
abstract: BACKGROUND
  There is greater awareness of the pathologic features and clinical implications of antibody-mediated rejection (AMR) after heart transplantation (HT). Yet, compared with adults, the lack of routine surveillance for AMR has limited the growth of evidence in the pediatric population. Herein, we compared outcomes of pediatric HT recipients with and without AMR.
  
  
  METHODS
  All recipients ≤18 years of age with at least 1 endomyocardial biopsy (EMB) between 1988 and 2009 were included in this study. Assessment for AMR was routine. AMR severity was assigned retrospectively using the proposed 2011 ISHLT grading schema for pathologic AMR (pAMR). Outcome comparisons were made between patients with histologic and immunopathologic evidence for AMR (pAMR 2), those with severe AMR (pAMR 3), and those without evidence of AMR (pAMR 0) or without both histologic and immunopathologic findings (pAMR 1).
  
  
  RESULTS
  Among 1,406 EMBs, pAMR 2 or higher was present in 258 (18%), occurring in 45 of 76 (59%) patients. Of the 17 episodes of pAMR 3 in 9 patients, 6 (35%) were sub-clinical. Mortality was not different between groups. Patients with at least 1 pAMR 3 episode had lower freedom from cardiovascular (CV) mortality or cardiac allograft vasculopathy within 5 years of HT than those without pAMR 3 (45% vs 91%, p < 0.001).
  
  
  CONCLUSIONS
  Biopsy findings of AMR (pAMR 2 or higher) are common after pediatric HT. Like cellular rejection, biopsy grading of AMR seems important to delineate those at risk of adverse events. Our results suggest that pAMR 3 is associated with worse CV outcomes. Widespread surveillance for pAMR with a uniform grading system is an important next step to further validate these findings in the pediatric HT population.
authors.affiliation: Division of Cardiology, University of Utah, Salt Lake City, Utah, USA. melanie.everitt@imail.org
authors.forename: Melanie D
authors.initials: MD
authors.lastname: Everitt
authors.forename: M Elizabeth H
authors.initials: ME
authors.lastname: Hammond
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Snow
authors.forename: Josef
authors.initials: J
authors.lastname: Stehlik
authors.forename: Monica P
authors.initials: MP
authors.lastname: Revelo
authors.forename: Dylan V
authors.initials: DV
authors.lastname: Miller
authors.forename: Aditya K
authors.initials: AK
authors.lastname: Kaza
authors.forename: Deborah
authors.initials: D
authors.lastname: Budge
authors.forename: Rami
authors.initials: R
authors.lastname: Alharethi
authors.forename: Kimberly M
authors.initials: KM
authors.lastname: Molina
authors.forename: Abdallah G
authors.initials: AG
authors.lastname: Kfoury
mesh_terms: D000293:Adolescent; D000906:Antibodies / Q000378:metabolism*; D001706:Biopsy; D002318:Cardiovascular Diseases / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology*; D006330:Heart Defects, Congenital / Q000601:surgery; D016027:Heart Transplantation / Q000276:immunology* / Q000401:mortality; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism; D007223:Infant; D007391:International Cooperation; D008297:Male; D009206:Myocardium / Q000276:immunology* / Q000473:pathology*; D017063:Outcome Assessment, Health Care; D012189:Retrospective Studies; D012307:Risk Factors; D012955:Societies, Medical; D015996:Survival Rate
chemical_list: D000906:Antibodies; D007136:Immunoglobulins