title: Donor-Specific Anti-HLA Antibodies and Endothelial C4d Deposition-Association With Chronic Liver Allograft Failure.
abstract: BACKGROUND
  The significance of humoral immune response for allograft survival after liver transplantation (LT) is still a matter of debate. The aim of this cross-sectional study was to assess immunological and clinical factors associated with advanced fibrosis (F3-F4) and chronic graft failure in LT recipients.
  
  
  METHODS
  Serum samples from 174 patients prospectively enrolled and followed up for 12 months were tested for anti-HLA antibodies and compared against donor HLA types. Immunohistochemical C4d staining was performed on formalin-fixed, paraffin-embedded liver tissue.
  
  
  RESULTS
  Mean time period from LT to enrollment was 66.9 ± 51.9 months. Independent predictive factors for graft failure included donor-positive cytomegalovirus serostatus (P = 0.02), donor-specific antibodies (DSA) against HLA class II (P = 0.03), donor age (P = 0.01), hepatitis C virus allograft reinfection (P = 0.0008), and biliary complications (P = 0.003). HLA class II DSA and HLA class I antibody positivity, hepatitis C virus reinfection, and mycophenolate mofetil-free regimens were significant risk factors for advanced fibrosis after LT. There was a significant association between C4d deposition on allograft endothelial cells and presence of class II DSA (P < 0.0001). Patients with C4d deposits had a 4.3 times higher risk of graft failure than those with negative staining and a significantly lower median time to graft failure (94.6 months [range, 3.6-158.9 months] vs 176.4 months [range, 9.4-217.8 months], P < 0.0001).
  
  
  CONCLUSIONS
  Screening for HLA DSA might be useful for early identification of LT recipients at increased risk of graft failure who could benefit from closer surveillance and tailored immunosuppressive regimens.
authors.affiliation: 1 Department of Transplant Medicine, University Hospital Münster, Münster, Germany. 2 Department of General, Visceral and Transplantation Surgery, University Hospital Essen, Essen, Germany. 3 Fundeni Clinical Institute of Digestive Diseases and Liver Transplantation, Bucharest, Romania. 4 Department of Gastroenterology and Hepatology, University Hospital Essen, Essen, Germany. 5 Institute for Transfusion Medicine, University Hospital Essen, Essen, Germany. 6 Institute of Pathology, University Hospital Essen, Essen, Germany.
authors.forename: Speranta
authors.initials: S
authors.lastname: Iacob
authors.forename: Vito R
authors.initials: VR
authors.lastname: Cicinnati
authors.forename: Monika
authors.initials: M
authors.lastname: Lindemann
authors.forename: Falko M
authors.initials: FM
authors.lastname: Heinemann
authors.forename: Arnold
authors.initials: A
authors.lastname: Radtke
authors.forename: Gernot M
authors.initials: GM
authors.lastname: Kaiser
authors.forename: Iyad
authors.initials: I
authors.lastname: Kabar
authors.forename: Hartmut H J
authors.initials: HH
authors.lastname: Schmidt
authors.forename: Hideo A
authors.initials: HA
authors.lastname: Baba
authors.forename: Susanne
authors.initials: S
authors.lastname: Beckebaum
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D015935:Complement C4b / Q000378:metabolism*; D003430:Cross-Sectional Studies; D042783:Endothelial Cells / Q000276:immunology*; D005260:Female; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D056724:Immunity, Humoral; D007150:Immunohistochemistry; D007518:Isoantibodies / Q000097:blood*; D008099:Liver / Q000276:immunology* / Q000473:pathology; D008103:Liver Cirrhosis / Q000097:blood / Q000175:diagnosis / Q000276:immunology*; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000378:metabolism*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012307:Risk Factors; D013997:Time Factors; D017211:Treatment Failure
chemical_list: D015415:Biomarkers; D006680:HLA Antigens; D007518:Isoantibodies; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d