title: Donor-specific HLA Antibodies Are Associated With Late Allograft Dysfunction After Pediatric Liver Transplantation.
abstract: BACKGROUND
  The role of donor-specific HLA antibodies (DSA) after pediatric liver transplantation (LTx) is not clearly established. We completed a cross-sectional study to characterize DSA in long-term survivors of pediatric LTx and assess the impact of C1q-binding DSA on allograft outcomes.
  
  
  METHODS
  Serum samples were collected at routine clinic visits from 50 pediatric LTx recipients classified into 3 clinical phenotypes: nontolerant (n = 18) with de novo autoimmune hepatitis (DAIH) and/or late acute cellular rejection (ACR); stable (n = 25) on maintenance tacrolimus; operationally tolerant (n = 7). Samples were blinded, and antibody detection was performed using Luminex single antigen class I and II beads. Patients with positive DSA were tested for C1q-binding DSA.
  
  
  RESULTS
  DSA were detected in 54% (n = 27) of the patients, with the majority directed at HLA class II antigens (DR, 41%; DQ, 53%). Patients with DSA were younger at the time of LTx (P = 0.016) and time of study (P = 0.024). Mean aspartate aminotransferase, alanine aminotransferase, total bilirubin, and gamma glutamyl transferase were higher in DSA-positive patients, though did not reach statistical significance. Nontolerant patients were significantly more likely to have DQ DSA (61%) compared to stable (20%) and tolerant (29%) patients (P = 0.021). The nontolerant phenotype was associated with DSA and C1q-binding DSA, with odds ratios of 13 (P = 0.015) and 8.6 (P = 0.006), respectively. The presence of DQ DSA was associated with DAIH and late ACR, with odds ratios of 12.5 (P = 0.004) and 10.8 (P = 0.006), respectively.
  
  
  CONCLUSIONS
  Allograft dysfunction is not always evident in patients with DSA, but DQ DSA are strongly associated with DAIH, late ACR, and chronic rejection.
authors.affiliation: 1 Pediatric Gastroenterology, Hepatology, and Nutrition, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA. 2 Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA. 3 Immunogenetics Center, University of California, Los Angeles, Los Angeles, CA. 4 Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA.
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Wozniak
authors.forename: Michelle J
authors.initials: MJ
authors.lastname: Hickey
authors.forename: Robert S
authors.initials: RS
authors.lastname: Venick
authors.forename: Jorge H
authors.initials: JH
authors.lastname: Vargas
authors.forename: Douglas G
authors.initials: DG
authors.lastname: Farmer
authors.forename: Ronald W
authors.initials: RW
authors.lastname: Busuttil
authors.forename: Sue V
authors.initials: SV
authors.lastname: McDiarmid
authors.forename: Elaine F
authors.initials: EF
authors.lastname: Reed
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000367:Age Factors; D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D015922:Complement C1q / Q000276:immunology; D003430:Cross-Sectional Studies; D005260:Female; D006084:Graft Rejection / Q000097:blood / Q000175:diagnosis / Q000276:immunology* / Q000517:prevention & control; D006085:Graft Survival; D006680:HLA Antigens / Q000276:immunology*; D006683:HLA-DQ Antigens / Q000276:immunology; D019693:Hepatitis, Autoimmune / Q000097:blood / Q000175:diagnosis / Q000276:immunology* / Q000517:prevention & control; D006648:Histocompatibility; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007223:Infant; D007231:Infant, Newborn; D007518:Isoantibodies / Q000097:blood*; D016031:Liver Transplantation / Q000009:adverse effects*; D016015:Logistic Models; D008297:Male; D015999:Multivariate Analysis; D016017:Odds Ratio; D010641:Phenotype; D012307:Risk Factors; D016559:Tacrolimus / Q000627:therapeutic use; D013997:Time Factors; D023001:Transplantation Tolerance / Q000187:drug effects; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers; D006680:HLA Antigens; D006683:HLA-DQ Antigens; D007166:Immunosuppressive Agents; D007518:Isoantibodies; D015922:Complement C1q; D016559:Tacrolimus