title: Donor-specific antibodies: can they predict C4d deposition in pediatric heart recipients?
abstract: There is limited evidence regarding the utility of circulating DSA in surveillance for AMR of pediatric heart recipients. Our hypothesis is that quantitation of DSA improves their power for predicting a C4d+, an integral component in the current diagnostic criteria of AMR. All pediatric recipients transplanted between 10/2005 and 1/2011 were retrospectively reviewed for DSA determined within 48 h of EMB. C4d+ was defined as >25% endothelial cell staining by immunohistochemical methods. A total of 183 paired DSA-EMB determinations were identified in 60 patients, a median of three paired studies per patient (range: 1-9). DSA were detected in 60 of these determinations. A receiver-operating characteristic plot identified a threshold single-antibody MFI of >6000 that strongly correlated with C4d+ (p < 0.0001) with a high negative predictive value (0.97) and specificity (0.95). The sensitivity and positive predictive values were 0.71 and 0.60, respectively. The predictive power of single-antigen DSA for C4d deposition was improved in pediatric heart recipients using an institution-specific MFI threshold value. In post-transplant care, quantitative DSA should be an essential component in the surveillance for AMR.
authors.affiliation: University of Washington/Seattle Children's Hospital, Seattle, WA, USA. david.peng@me.com
authors.forename: David M
authors.initials: DM
authors.lastname: Peng
authors.forename: Yuk M
authors.initials: YM
authors.lastname: Law
authors.forename: Mariska S
authors.initials: MS
authors.lastname: Kemna
authors.forename: Paul
authors.initials: P
authors.lastname: Warner
authors.forename: Karen
authors.initials: K
authors.lastname: Nelson
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Boucek
mesh_terms: D000293:Adolescent; D000906:Antibodies / Q000737:chemistry*; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D015935:Complement C4b / Q000737:chemistry*; D005260:Female; D006084:Graft Rejection; D006680:HLA Antigens / Q000276:immunology*; D006333:Heart Failure / Q000276:immunology* / Q000628:therapy*; D016027:Heart Transplantation / Q000379:methods*; D006650:Histocompatibility Testing; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D010446:Peptide Fragments / Q000737:chemistry*; D011237:Predictive Value of Tests; D012372:ROC Curve; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D014019:Tissue Donors; D016896:Treatment Outcome
chemical_list: D000906:Antibodies; D006680:HLA Antigens; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d
keywords: anti-HLA antibody; antibody mediated rejection; biopsy; heart transplantation; pediatric heart transplant